Pub Date : 2007-01-01DOI: 10.1101/087969767.48.401
R. Schneider, N. Sonenberg
Translational control has an important role in key physiological pathways that have a direct impact on cancer development and progression. These include pathways for cell proliferation and growth, cellular responses to stresses such as hypoxia and nutritional deprivation, and stimulation by mitogenic signals (for previous reviews, see Dua et al. 2001; Meric and Hunt 2002; Rosenwald 2004; Holcik and Sonenberg 2005). Consequently, regulation of protein synthesis has emerged as an important component of cancer etiology, both at the level of global control of the proteome and for selective translation of specific mRNAs and classes of mRNAs. What is surprising is how long it has taken to appreciate the central importance and elucidate the key mechanisms of translational control in cancer development and progression. Despite the infancy of this field of research, it is already apparent that translational control of cancer is multifaceted, presenting modifications unique to different types of cancers, as well as different stages and grades of disease. Changes in translation associated with cancer development and progression observed to date involve altered expression of translation components, including translation factors, ribosomes, translation factor regulatory proteins, and tRNAs; altered expression and translation of specific mRNAs; and altered activity of signal transduction pathways that control the activity of protein synthesis, both overall and of individual mRNAs. These changes are manifested in a variety of ways, including up-regulation of global protein synthesis, increased translation of individual mRNAs, and selective translation of antiapoptotic, proangiogenic, proproliferative, and hypoxia-mediated mRNAs. Other transformation-associated changes in translation are...
翻译控制在直接影响癌症发生和进展的关键生理途径中起着重要作用。这些包括细胞增殖和生长的途径，细胞对缺氧和营养剥夺等应激的反应，以及有丝分裂信号的刺激(关于以前的综述，见Dua等人2001;Meric and Hunt 2002;罗森沃尔德2004;Holcik and Sonenberg 2005)。因此，蛋白质合成的调控已经成为癌症病因学的一个重要组成部分，无论是在蛋白质组的全局控制水平上，还是在特定mrna和mrna类别的选择性翻译水平上。令人惊讶的是，人们花了很长时间才认识到翻译控制在癌症发生和进展中的核心重要性，并阐明了翻译控制的关键机制。尽管这一研究领域尚处于起步阶段，但很明显，癌症的转译控制是多方面的，针对不同类型的癌症以及不同的疾病阶段和等级呈现出独特的修饰。迄今为止观察到的与癌症发生和进展相关的翻译变化涉及翻译成分的表达改变，包括翻译因子、核糖体、翻译因子调节蛋白和trna;特异性mrna表达和翻译的改变;以及控制蛋白质合成活性的信号转导途径的活性改变，包括整体和单个mrna。这些变化以多种方式表现出来，包括整体蛋白合成的上调，单个mrna的翻译增加，以及抗凋亡、促血管生成、促增殖和缺氧介导的mrna的选择性翻译。翻译中与转换相关的其他更改有……
{"title":"15 Translational Control in Cancer Development and Progression","authors":"R. Schneider, N. Sonenberg","doi":"10.1101/087969767.48.401","DOIUrl":"https://doi.org/10.1101/087969767.48.401","url":null,"abstract":"Translational control has an important role in key physiological pathways that have a direct impact on cancer development and progression. These include pathways for cell proliferation and growth, cellular responses to stresses such as hypoxia and nutritional deprivation, and stimulation by mitogenic signals (for previous reviews, see Dua et al. 2001; Meric and Hunt 2002; Rosenwald 2004; Holcik and Sonenberg 2005). Consequently, regulation of protein synthesis has emerged as an important component of cancer etiology, both at the level of global control of the proteome and for selective translation of specific mRNAs and classes of mRNAs. What is surprising is how long it has taken to appreciate the central importance and elucidate the key mechanisms of translational control in cancer development and progression. Despite the infancy of this field of research, it is already apparent that translational control of cancer is multifaceted, presenting modifications unique to different types of cancers, as well as different stages and grades of disease. Changes in translation associated with cancer development and progression observed to date involve altered expression of translation components, including translation factors, ribosomes, translation factor regulatory proteins, and tRNAs; altered expression and translation of specific mRNAs; and altered activity of signal transduction pathways that control the activity of protein synthesis, both overall and of individual mRNAs. These changes are manifested in a variety of ways, including up-regulation of global protein synthesis, increased translation of individual mRNAs, and selective translation of antiapoptotic, proangiogenic, proproliferative, and hypoxia-mediated mRNAs. Other transformation-associated changes in translation are...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"3 1","pages":"401-431"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89623640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-01-01DOI: 10.1101/087969767.48.459
S. Kozma, S. Um, G. Thomas
For some time it has been recognized not only that protein synthesis is regulated by growth factors and hormonal signaling (Shi et al. 2003), but that the translation machinery is also specifically affected by nutrient levels (Clemens et al. 1980; Pain et al. 1980). These stimuli modulate both the global synthesis of proteins and the selective translation of specific mRNAs. Thus, given the impact of nutrient supply and endocrine signaling on protein synthesis, it is logical to presume that pathological conditions affecting nutrient homeostasis would result in major deregulation of protein synthesis. Currently, the most prevalent homeostatic dis-order is the metabolic syndrome, defined as a cluster of pathologies that always includes obesity, plus at least two of the following factors: raised serum triglyceride levels, reduced high-density-lipoprotein cholesterol levels, raised blood pressure, and raised fasting plasma glucose. The recent dramatic increase in the incidence of obesity has strongly contributed to an escalation of the metabolic syndrome manifestations in Western societies. It is believed that the increase in obesity derives from the fact that during evolution, food scarcity led to the development of dominant genetic traits to secure and manage caloric intake (Neel 1999). In Western societies, food availability, which increased dramatically in the 1950s, began to reveal these calorie-securing traits, and obesity emerged as a prevalent disorder that has since reached epidemic proportions. The nutrient overload resulting from increased food intake is being further accentuated by a decrease in physical activity and a demographic shift to an aging population (Pi-Sunyer 2002).
一段时间以来，人们已经认识到，不仅蛋白质合成受生长因子和激素信号的调节(Shi et al. 2003)，而且翻译机制也特别受到营养水平的影响(Clemens et al. 1980;Pain et al. 1980)。这些刺激调节了蛋白质的整体合成和特定mrna的选择性翻译。因此，考虑到营养供应和内分泌信号对蛋白质合成的影响，我们可以合理地假设，影响营养稳态的病理状况将导致蛋白质合成的严重失调。目前，最普遍的体内平衡紊乱是代谢综合征，它被定义为一组病理，通常包括肥胖，加上以下至少两种因素:血清甘油三酯水平升高、高密度脂蛋白胆固醇水平降低、血压升高和空腹血糖升高。近年来肥胖发病率的急剧增加，极大地促进了西方社会代谢综合征的升级。人们认为，肥胖的增加源于这样一个事实，即在进化过程中，食物短缺导致了显性遗传性状的发展，以确保和管理热量摄入(Neel 1999)。在西方社会，食物供应在20世纪50年代急剧增加，开始显示出这些卡路里安全的特征，肥胖成为一种普遍的疾病，从那时起就达到了流行病的程度。由于身体活动的减少和人口向老龄化的转变，食物摄入增加导致的营养过剩进一步加剧(Pi-Sunyer 2002)。
{"title":"17 Translational Control in Metabolic Diseases: The Role of mTOR Signaling in Obesity and Diabetes","authors":"S. Kozma, S. Um, G. Thomas","doi":"10.1101/087969767.48.459","DOIUrl":"https://doi.org/10.1101/087969767.48.459","url":null,"abstract":"For some time it has been recognized not only that protein synthesis is regulated by growth factors and hormonal signaling (Shi et al. 2003), but that the translation machinery is also specifically affected by nutrient levels (Clemens et al. 1980; Pain et al. 1980). These stimuli modulate both the global synthesis of proteins and the selective translation of specific mRNAs. Thus, given the impact of nutrient supply and endocrine signaling on protein synthesis, it is logical to presume that pathological conditions affecting nutrient homeostasis would result in major deregulation of protein synthesis. Currently, the most prevalent homeostatic dis-order is the metabolic syndrome, defined as a cluster of pathologies that always includes obesity, plus at least two of the following factors: raised serum triglyceride levels, reduced high-density-lipoprotein cholesterol levels, raised blood pressure, and raised fasting plasma glucose. The recent dramatic increase in the incidence of obesity has strongly contributed to an escalation of the metabolic syndrome manifestations in Western societies. It is believed that the increase in obesity derives from the fact that during evolution, food scarcity led to the development of dominant genetic traits to secure and manage caloric intake (Neel 1999). In Western societies, food availability, which increased dramatically in the 1950s, began to reveal these calorie-securing traits, and obesity emerged as a prevalent disorder that has since reached epidemic proportions. The nutrient overload resulting from increased food intake is being further accentuated by a decrease in physical activity and a demographic shift to an aging population (Pi-Sunyer 2002).","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"13 1","pages":"459-483"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89178798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-01-01DOI: 10.1101/087969767.48.775
E. Shoubridge, F. Sasarman
Most eukaryotic cells rely on oxidative phosphorylation for cellular ATP production. The machinery for oxidative phosphorylation consists of five large hetero-oligomeric enzyme complexes, located in the inner mitochondrial membrane. The majority of the approximately 85 structural components of this system are encoded in the nuclear genome, but a small number of essential protein subunits—13 in mammals—have been retained on the mitochondrial genome (mtDNA), and these are synthesized on a dedicated protein translation apparatus in the mitochondrial matrix. All of the proteins necessary for the replication, transcription, and translation of the genes encoded in mtDNA are encoded in the nuclear genome. This genetic investment is far out of proportion to the number of proteins involved, and it is likely that a small, semiautonomous mitochondrial genome has persisted because the proteins it encodes are hydrophobic proteins that need to be cotranslationally inserted into the inner mitochondrial membrane during assembly of the oxidative phosphorylation complexes. As might be expected from the α- proteobacterial origins of mitochondria, many of the features of mitochondrial translation are similar to those found in prokaryotes. In this chapter, we review the organization and control of mitochondrial translation, with a particular emphasis on the system in mammals and on mechanisms of disease. ORGANIZATION OF THE MAMMALIAN MITOCHONDRIAL TRANSLATION SYSTEM Mammalian mtDNA is a small (~16.5 kb) double-stranded circular genome that codes for 13 proteins, 22 tRNAs, and 2 rRNAs. It contains no introns, and the genetic code is different from the universal code: Nuclear arginine (AGA, AGG)...
{"title":"27 Mitochondrial Translation and Human Disease","authors":"E. Shoubridge, F. Sasarman","doi":"10.1101/087969767.48.775","DOIUrl":"https://doi.org/10.1101/087969767.48.775","url":null,"abstract":"Most eukaryotic cells rely on oxidative phosphorylation for cellular ATP production. The machinery for oxidative phosphorylation consists of five large hetero-oligomeric enzyme complexes, located in the inner mitochondrial membrane. The majority of the approximately 85 structural components of this system are encoded in the nuclear genome, but a small number of essential protein subunits—13 in mammals—have been retained on the mitochondrial genome (mtDNA), and these are synthesized on a dedicated protein translation apparatus in the mitochondrial matrix. All of the proteins necessary for the replication, transcription, and translation of the genes encoded in mtDNA are encoded in the nuclear genome. This genetic investment is far out of proportion to the number of proteins involved, and it is likely that a small, semiautonomous mitochondrial genome has persisted because the proteins it encodes are hydrophobic proteins that need to be cotranslationally inserted into the inner mitochondrial membrane during assembly of the oxidative phosphorylation complexes. As might be expected from the α- proteobacterial origins of mitochondria, many of the features of mitochondrial translation are similar to those found in prokaryotes. In this chapter, we review the organization and control of mitochondrial translation, with a particular emphasis on the system in mammals and on mechanisms of disease. ORGANIZATION OF THE MAMMALIAN MITOCHONDRIAL TRANSLATION SYSTEM Mammalian mtDNA is a small (~16.5 kb) double-stranded circular genome that codes for 13 proteins, 22 tRNAs, and 2 rRNAs. It contains no introns, and the genetic code is different from the universal code: Nuclear arginine (AGA, AGG)...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"104 1","pages":"775-801"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88383218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Standard translation initiation in eukaryotes is the process that leads to assembly of an 80S ribosome on an mRNA in which the initiation codon is base-paired to the CAU anticodon of aminoacylated initiator methionyl-transfer RNA (Met-tRNA i Met ) in the ribosomal peptidyl (P) site. The process requires separated small (40S) and large (60S) ribosomal subunits and involves at least 12 eukaryotic initiation factors (eIFs) and the binding and hydrolysis of ATP and GTP. The resulting 80S initiation complex is competent to enter the elongation phase of translation. This chapter describes the canonical mechanism of 5′-end-dependent initiation, with a bias toward the initiation process in higher eukaryotes. This process differs in detail from that in plants and yeast, in which the subunit structure and composition of some factors differ substantially. For a more detailed review of initiation in yeast and in plants, see Chapters 9 and 26, respectively. For a review of mechanisms dependent on internal ribosome entry, see Chapters 5 and 6. STRUCTURE OF EUKARYOTIC CYTOPLASMIC mRNAs The translational efficiency of eukaryotic mRNAs is limited by the rate of initiation (see, e.g., Palmiter 1972), which is in turn determined by structural features of mRNAs that influence ribosomal recruitment, scanning to the initiation codon, and initiation codon recognition. Eukaryotic mRNAs associate dynamically with proteins that mediate nuclear export, subcellular localization, stability, and translational repression, and therefore exist in cells as messenger ribonucleoproteins (mRNPs) rather than as free polynucleotides. The influence of mRNP proteins on initiation is outside the scope of this review. Almost...
真核生物的标准翻译起始是导致80S核糖体在mRNA上组装的过程，其中起始密码子与核糖体肽基(P)位点上氨基酰化启动物甲硫基转移RNA (Met- trna i Met)的CAU反密码子碱基配对。该过程需要分离小(40S)和大(60S)核糖体亚基，涉及至少12个真核起始因子(eIFs)以及ATP和GTP的结合和水解。由此产生的80S起始复合物能够进入翻译的延伸期。本章描述了5 '端依赖起始的典型机制，侧重于高等真核生物的起始过程。这一过程与植物和酵母中的过程在细节上有所不同，在植物和酵母中，亚基结构和一些因素的组成有很大的不同。关于酵母起始和植物起始的更详细的综述，分别见第9章和第26章。有关内部核糖体进入机制的回顾，请参见第5章和第6章。真核细胞质mrna的翻译效率受起始速率的限制(参见Palmiter 1972)，而起始速率又由mrna的结构特征决定，这些结构特征会影响核糖体的招募、对起始密码子的扫描以及起始密码子的识别。真核mrna与介导核输出、亚细胞定位、稳定性和翻译抑制的蛋白质动态关联，因此作为信使核糖核蛋白(mRNPs)而不是作为自由多核苷酸存在于细胞中。mRNP蛋白对起始的影响不在本文的讨论范围之内。几乎……
{"title":"4 The Mechanism of Translation Initiation in Eukaryotes","authors":"T. Pestova, J. Lorsch, C. Hellen","doi":"10.1101/087969767.48.87","DOIUrl":"https://doi.org/10.1101/087969767.48.87","url":null,"abstract":"Standard translation initiation in eukaryotes is the process that leads to assembly of an 80S ribosome on an mRNA in which the initiation codon is base-paired to the CAU anticodon of aminoacylated initiator methionyl-transfer RNA (Met-tRNA i Met ) in the ribosomal peptidyl (P) site. The process requires separated small (40S) and large (60S) ribosomal subunits and involves at least 12 eukaryotic initiation factors (eIFs) and the binding and hydrolysis of ATP and GTP. The resulting 80S initiation complex is competent to enter the elongation phase of translation. This chapter describes the canonical mechanism of 5′-end-dependent initiation, with a bias toward the initiation process in higher eukaryotes. This process differs in detail from that in plants and yeast, in which the subunit structure and composition of some factors differ substantially. For a more detailed review of initiation in yeast and in plants, see Chapters 9 and 26, respectively. For a review of mechanisms dependent on internal ribosome entry, see Chapters 5 and 6. STRUCTURE OF EUKARYOTIC CYTOPLASMIC mRNAs The translational efficiency of eukaryotic mRNAs is limited by the rate of initiation (see, e.g., Palmiter 1972), which is in turn determined by structural features of mRNAs that influence ribosomal recruitment, scanning to the initiation codon, and initiation codon recognition. Eukaryotic mRNAs associate dynamically with proteins that mediate nuclear export, subcellular localization, stability, and translational repression, and therefore exist in cells as messenger ribonucleoproteins (mRNPs) rather than as free polynucleotides. The influence of mRNP proteins on initiation is outside the scope of this review. Almost...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"1 1","pages":"87-128"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77410334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-01-01DOI: 10.1101/087969767.48.601
T. Herbert, C. Proud
The factors involved in translation elongation are subject to sophisticated control mechanisms that come into play under a wide variety of conditions. Even though translation is most frequently controlled during the initiation phase (Chapter 1) and the regulatory mechanisms impinging on the initiation steps have received considerable attention (reviewed in several chapters of this book), accumulating information points to the elongation phase as a target for controls under defined circumstances. In this chapter, we focus on recent developments in understanding the control of elongation in mammalian cells. As a special case, we also discuss cotranslational protein targeting, a cellular process involving the control of elongation on an important class of mRNAs. REGULATION OF TRANSLATION ELONGATION The mechanism of peptide-chain elongation and the functions of translation elongation factors are described in Chapters 2 and 3. In addition, detailed aspects of the structure and function of eukaryotic elongation factor 2 (eEF2) are the subject of a recent informative review (Jorgensen et al. 2006). eEF2 is a phosphoprotein in mammalian cells, and most of the recent advances relate to the regulation of eEF2 and its cognate kinase, eEF2 kinase. eEF1A and eEF1B also are phosphoproteins and have been discussed in earlier reviews on this subject (Proud 2000; Traugh 2001; Browne and Proud 2002; Le Sourd et al. 2006). Significance of eEF2 Phosphorylation for the Control of Protein Synthesis Under a diverse range of conditions, the phosphorylation state of eEF2 changes in directions consistent with its having a role in regulating protein synthesis; i.e.,...
涉及平移伸长的因素受到复杂的控制机制的影响，这些机制在各种各样的条件下发挥作用。尽管翻译最常在起始阶段受到控制(第1章)，并且影响起始步骤的调控机制受到了相当大的关注(在本书的几章中进行了回顾)，但积累的信息表明，在特定情况下，延伸阶段是控制的目标。在本章中，我们将重点介绍哺乳动物细胞伸长控制的最新进展。作为一种特殊情况，我们还讨论了共翻译蛋白靶向，这是一种涉及控制一类重要mrna延伸的细胞过程。肽链延伸的机制和翻译延伸因子的功能在第二章和第三章中进行了描述。此外，真核延伸因子2 (eEF2)的结构和功能的详细方面是最近一篇信息性综述的主题(Jorgensen et al. 2006)。eEF2是哺乳动物细胞中的一种磷酸化蛋白，最近的研究进展大多与eEF2及其同源激酶eEF2激酶的调控有关。eEF1A和eEF1B也是磷酸化蛋白，并已在该主题的早期评论中讨论过(Proud 2000;Traugh 2001;Browne and Proud 2002;Le Sourd et al. 2006)。eEF2磷酸化对蛋白质合成的控制意义在多种条件下，eEF2磷酸化状态的变化方向与其调节蛋白质合成的作用一致;也就是说,…
{"title":"21 Regulation of Translation Elongation and the Cotranslational Protein Targeting Pathway","authors":"T. Herbert, C. Proud","doi":"10.1101/087969767.48.601","DOIUrl":"https://doi.org/10.1101/087969767.48.601","url":null,"abstract":"The factors involved in translation elongation are subject to sophisticated control mechanisms that come into play under a wide variety of conditions. Even though translation is most frequently controlled during the initiation phase (Chapter 1) and the regulatory mechanisms impinging on the initiation steps have received considerable attention (reviewed in several chapters of this book), accumulating information points to the elongation phase as a target for controls under defined circumstances. In this chapter, we focus on recent developments in understanding the control of elongation in mammalian cells. As a special case, we also discuss cotranslational protein targeting, a cellular process involving the control of elongation on an important class of mRNAs. REGULATION OF TRANSLATION ELONGATION The mechanism of peptide-chain elongation and the functions of translation elongation factors are described in Chapters 2 and 3. In addition, detailed aspects of the structure and function of eukaryotic elongation factor 2 (eEF2) are the subject of a recent informative review (Jorgensen et al. 2006). eEF2 is a phosphoprotein in mammalian cells, and most of the recent advances relate to the regulation of eEF2 and its cognate kinase, eEF2 kinase. eEF1A and eEF1B also are phosphoproteins and have been discussed in earlier reviews on this subject (Proud 2000; Traugh 2001; Browne and Proud 2002; Le Sourd et al. 2006). Significance of eEF2 Phosphorylation for the Control of Protein Synthesis Under a diverse range of conditions, the phosphorylation state of eEF2 changes in directions consistent with its having a role in regulating protein synthesis; i.e.,...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"23 1","pages":"601-624"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84790023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-01-01DOI: 10.1101/087969819.49.647
R. Greenspan
In the mid-1980s, when the study of molecular mechanisms in the nervous system first emerged, comparisons between vertebrates and invertebrates began to appear. A fly on the wall of a molecular neurobiology meeting at that time would have heard much talk of “higher” and “lower” organisms. He would have concluded that his cousins, the fruit flies, had evolved from nematodes, and similarly, that frogs had evolved from fruit flies, and likewise mice from frogs. These formulations recalled the Great Chain of Being (Fig. 1), an idea that had strong historical roots dating back to Plato and Aristotle. At one particular neurobiology meeting, a developmental biologist with a strong evolutionary background was asked to give a short summary of phylogeny for the assembled group. He described the two major branches of metazoan evolution, protostomes and deuterostomes (Fig. 1), and tried his best to undo the concepts of “higher” versus “lower,” as well as of a single, continuous line of descent. Over the next two days, it was clear that his discourse was taken as meaning that there was not a single Great Chain of Being; instead, there were actually two. All extant species are certainly not, in fact, evolved directly from each other, but instead represent the currently living products of many different lineage branches. If this is so, then what kinds of meaningful comparisons can we make and what can they tell us? Homologies have traditionally been the goal of evolutionary comparisons. Originally, this meant morphological homology of a structure...
{"title":"Afterword Universality and Brain Mechanisms","authors":"R. Greenspan","doi":"10.1101/087969819.49.647","DOIUrl":"https://doi.org/10.1101/087969819.49.647","url":null,"abstract":"In the mid-1980s, when the study of molecular mechanisms in the nervous system first emerged, comparisons between vertebrates and invertebrates began to appear. A fly on the wall of a molecular neurobiology meeting at that time would have heard much talk of “higher” and “lower” organisms. He would have concluded that his cousins, the fruit flies, had evolved from nematodes, and similarly, that frogs had evolved from fruit flies, and likewise mice from frogs. These formulations recalled the Great Chain of Being (Fig. 1), an idea that had strong historical roots dating back to Plato and Aristotle. At one particular neurobiology meeting, a developmental biologist with a strong evolutionary background was asked to give a short summary of phylogeny for the assembled group. He described the two major branches of metazoan evolution, protostomes and deuterostomes (Fig. 1), and tried his best to undo the concepts of “higher” versus “lower,” as well as of a single, continuous line of descent. Over the next two days, it was clear that his discourse was taken as meaning that there was not a single Great Chain of Being; instead, there were actually two. All extant species are certainly not, in fact, evolved directly from each other, but instead represent the currently living products of many different lineage branches. If this is so, then what kinds of meaningful comparisons can we make and what can they tell us? Homologies have traditionally been the goal of evolutionary comparisons. Originally, this meant morphological homology of a structure...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"17 1","pages":"647-649"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85058574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
My coeditor, Ralph Greenspan, and I have decided, rather than to coauthor a preface to this book, to act as bookends, with Ralph writing the Afterword and me writing the Foreword. This does not reflect any disagreement in view, but instead, complementary perspectives. Ralph has the point of view of a professional scientist in the field, and I have the point of view of a professional editor who is most definitely not a specialist, but who finds the field fascinating. Before explaining the rationale and aims of this book, it might be worth giving a bit of background-the views that have informed our approach to the subject.We share the opinion that the molecular revolution which began in the 1950s has over-skewed biology somewhat; the insights into fundamental processes that have been made possible by this revolution are remarkable, but they have tended to foster the view that the main point of biology is to elucidate molecular mechanisms. In the extreme view, a description of any biological phenomenon becomes a mere prelude to analysis by a now well-trod route: Screen for genetic variants where the phenomenon at issue is perturbed; clone the gene; sequence the gene; analyze its product; and so on. This approach has proved tremendously successful in many areas of biology, particularly cellular and developmental biology. Indeed, when the study of the molecular biology of metazoan organisms began in earnest in the 1970s and early 1980s, it was not clear that it would prove quite so...
{"title":"Preface/Front Matter","authors":"G. North","doi":"10.1101/087969819.49.i","DOIUrl":"https://doi.org/10.1101/087969819.49.i","url":null,"abstract":"My coeditor, Ralph Greenspan, and I have decided, rather than to coauthor a preface to this book, to act as bookends, with Ralph writing the Afterword and me writing the Foreword. This does not reflect any disagreement in view, but instead, complementary perspectives. Ralph has the point of view of a professional scientist in the field, and I have the point of view of a professional editor who is most definitely not a specialist, but who finds the field fascinating. Before explaining the rationale and aims of this book, it might be worth giving a bit of background-the views that have informed our approach to the subject.We share the opinion that the molecular revolution which began in the 1950s has over-skewed biology somewhat; the insights into fundamental processes that have been made possible by this revolution are remarkable, but they have tended to foster the view that the main point of biology is to elucidate molecular mechanisms. In the extreme view, a description of any biological phenomenon becomes a mere prelude to analysis by a now well-trod route: Screen for genetic variants where the phenomenon at issue is perturbed; clone the gene; sequence the gene; analyze its product; and so on. This approach has proved tremendously successful in many areas of biology, particularly cellular and developmental biology. Indeed, when the study of the molecular biology of metazoan organisms began in earnest in the 1970s and early 1980s, it was not clear that it would prove quite so...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73177817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-01-01DOI: 10.1101/087969819.49.155
D. Robert, R. Hoy
Evolution has endowed insects with an extraordinary capacity for miniaturization. Virtually all aspects of insect biology convey the sense of successfully uniting form and function in exquisitely small, diverse, and sophisticated motor, sensory, and metabolic systems (Grimaldi and Engel 2005). The ability of insects to fly in an efficient and controlled manner well illustrates how, through evolution by natural selection, they adapted to solve what we consider serious problems of engineering. Insects are little marvels of “evolutionary engineering.” The seemingly boundless ingenuity and creativity of the process of evolutionary adaptation are also reflected in the sensory systems of insects. As we try to make clear in this chapter, hearing in insects is a sophisticated process; understanding its fundamental mechanisms and trying to understand its evolution present many challenges but are likely to be very rewarding. Perhaps because insects are so small, their ears have generally been considered to be simple compared to those of vertebrates. Anatomically, they may be simpler, but their capacity for sound reception and processing turns out to be remarkably elaborate (for reviews, see Fullard and Yack 1993; Hoy 1998; Robert and Gopfert 2002; Robert 2005; Hedwig 2006; Gopfert and Robert 2007). The ears of insects can be as sensitive and acute as their vertebrate counterparts (Webster et al. 1992; Hoy 1998). Indeed, in some cases their feats of detection surpass the capabilities of vertebrates (Robert and Gopfert 2002). For example, the ultrafast ears of the parasitoid fly Ormia ochracea can distinguish time differences in the arrival...
进化赋予了昆虫非凡的小型化能力。事实上，昆虫生物学的所有方面都传达了一种感觉，即在精巧、多样和复杂的运动、感觉和代谢系统中成功地统一了形式和功能(Grimaldi和Engel, 2005)。昆虫以有效和可控的方式飞行的能力很好地说明了，通过自然选择的进化，它们如何适应解决我们认为严重的工程问题。昆虫是“进化工程”的小小奇迹。进化适应过程中看似无穷无尽的独创性和创造力也反映在昆虫的感觉系统上。正如我们在本章中试图阐明的那样，昆虫的听觉是一个复杂的过程;理解它的基本机制并试图理解它的进化过程存在许多挑战，但可能是非常有益的。也许是因为昆虫很小，与脊椎动物的耳朵相比，它们的耳朵通常被认为是简单的。从解剖学上讲，它们可能更简单，但它们接收和处理声音的能力却非常复杂(有关评论，见Fullard和Yack 1993;霍伊1998;Robert and Gopfert 2002;罗伯特2005;海德薇格2006;Gopfert and Robert 2007)。昆虫的耳朵可以像它们的脊椎动物一样敏感和敏锐(Webster et al. 1992;霍伊1998)。事实上，在某些情况下，它们的探测能力超过了脊椎动物的能力(Robert and Gopfert 2002)。例如，拟寄生虫蝇Ormia ochracea的超快耳朵可以区分到达的时间差异……
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Proteins occupy a position high on the list of molecules important for life processes. They account for a large fraction of biological macromolecules—about 44% of the human body’s dry weight, for example (Davidson et al. 1973)—they catalyze most of the reactions on which life depends, and they serve numerous structural, transport, regulatory, and other roles in all organisms. Accordingly, a large proportion of the cell’s resources is devoted to translation. The magnitude of this commitment can be appreciated in genetic, biochemical, and cell biological terms. Translation is a sophisticated process requiring extensive biological machinery. One way to gauge the amount of genetic information needed to assemble the protein synthetic machinery is to compile a “parts list” of essential proteins and RNAs. Analyses of the genomes of several microorganisms have converged on similar estimates (Hutchison et al. 1999; Tamas et al. 2002; Kobayashi et al. 2003; Waters et al. 2003). These organisms get by with about 130 genes for components of the translation machinery, including about 90 protein-coding genes (specifying 50–60 ribosomal proteins, about 20 aminoacyl-tRNA synthetases, and 10–15 translation factors) and about 40 genes for ribosomal and transfer RNAs (rRNA and tRNAs). A somewhat larger number of genes are involved in eukaryotes, which have more ribosomal proteins and initiation factors, for example. Discounting genes that are dispensable for growth in the laboratory, it can be calculated that approximately 40% of the genes in a theoretical minimal cellular genome are devoted to the translation apparatus. This heavy...
蛋白质在对生命过程至关重要的分子列表中占有很高的位置。它们占生物大分子的很大一部分——例如，约占人体干重的44% (Davidson et al. 1973)——它们催化生命所依赖的大多数反应，它们在所有生物体中起着许多结构、运输、调节和其他作用。因此，细胞资源的很大一部分用于翻译。这种承诺的重要性可以从遗传学、生物化学和细胞生物学的角度来理解。翻译是一个复杂的过程，需要广泛的生物机制。衡量组装蛋白质合成机器所需的遗传信息数量的一种方法是编制一份必需蛋白质和rna的“零件清单”。对几种微生物基因组的分析也得出了类似的估计(Hutchison et al. 1999;Tamas et al. 2002;Kobayashi et al. 2003;沃特斯等人，2003)。这些生物体通过大约130个基因组成翻译机制，包括大约90个蛋白质编码基因(指定50-60个核糖体蛋白质，大约20个氨基酰基trna合成酶和10-15个翻译因子)和大约40个核糖体和转移rna (rRNA和tRNAs)基因。真核生物中涉及的基因数量要多一些，例如，真核生物有更多的核糖体蛋白质和起始因子。扣除实验室中生长所必需的基因，可以计算出，理论上最小细胞基因组中约有40%的基因用于翻译装置。这个重…
{"title":"1 Origins and Principles of Translational Control","authors":"M. Mathews, N. Sonenberg, J. Hershey","doi":"10.1101/087969767.48.1","DOIUrl":"https://doi.org/10.1101/087969767.48.1","url":null,"abstract":"Proteins occupy a position high on the list of molecules important for life processes. They account for a large fraction of biological macromolecules—about 44% of the human body’s dry weight, for example (Davidson et al. 1973)—they catalyze most of the reactions on which life depends, and they serve numerous structural, transport, regulatory, and other roles in all organisms. Accordingly, a large proportion of the cell’s resources is devoted to translation. The magnitude of this commitment can be appreciated in genetic, biochemical, and cell biological terms. Translation is a sophisticated process requiring extensive biological machinery. One way to gauge the amount of genetic information needed to assemble the protein synthetic machinery is to compile a “parts list” of essential proteins and RNAs. Analyses of the genomes of several microorganisms have converged on similar estimates (Hutchison et al. 1999; Tamas et al. 2002; Kobayashi et al. 2003; Waters et al. 2003). These organisms get by with about 130 genes for components of the translation machinery, including about 90 protein-coding genes (specifying 50–60 ribosomal proteins, about 20 aminoacyl-tRNA synthetases, and 10–15 translation factors) and about 40 genes for ribosomal and transfer RNAs (rRNA and tRNAs). A somewhat larger number of genes are involved in eukaryotes, which have more ribosomal proteins and initiation factors, for example. Discounting genes that are dispensable for growth in the laboratory, it can be calculated that approximately 40% of the genes in a theoretical minimal cellular genome are devoted to the translation apparatus. This heavy...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"42 1","pages":"1-40"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77735388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Translational regulation is based on modulation of translational function, most often involving the initiation phase. Not surprisingly, regulation of protein synthesis differs markedly between bacteria and eukarya, reflecting the many differences between their respective mechanisms of initiation. Although the structures of all ribosomes share commonly conserved cores, which are responsible for the main processes of translational elongation, many of the molecular components involved in translational initiation are specific to the different phylogenetic domains. These include the initiation factors, the Shine-Dalgarno sequence, formylation of the methionyl initiator tRNA, the ability to reinitiate on polycistronic mRNAs, and so on. Thus, it is not at all clear how far our knowledge of 70S (prokaryotic) ribosome structure will go toward providing insight into the mechanisms of eukaryotic translational regulation. Nevertheless, this information will help to understand prokaryotic initiation, and at least provide a starting point for interpreting the emerging structures of eukaryotic ribosomes. Most of the steps of protein synthesis appear to be based on RNA, including the many interactions between mRNA, tRNA, and rRNA that occur during the elongation phase. The roles of the proteins, such as the elongation factors and ribosomal proteins, may be to refine underlying RNA-based mechanisms, optimizing the speed and accuracy of translation. Translational initiation, at least in part, is therefore likely to involve modulation of RNA-based processes by proteins such as the initiation factors. We are beginning to understand how some of these processes work, from several decades of biochemical and genetic studies combined with the more recent...
{"title":"2 Structure of the Bacterial Ribosome and Some Implications for Translational Regulation","authors":"H. Noller","doi":"10.1101/087969767.48.41","DOIUrl":"https://doi.org/10.1101/087969767.48.41","url":null,"abstract":"Translational regulation is based on modulation of translational function, most often involving the initiation phase. Not surprisingly, regulation of protein synthesis differs markedly between bacteria and eukarya, reflecting the many differences between their respective mechanisms of initiation. Although the structures of all ribosomes share commonly conserved cores, which are responsible for the main processes of translational elongation, many of the molecular components involved in translational initiation are specific to the different phylogenetic domains. These include the initiation factors, the Shine-Dalgarno sequence, formylation of the methionyl initiator tRNA, the ability to reinitiate on polycistronic mRNAs, and so on. Thus, it is not at all clear how far our knowledge of 70S (prokaryotic) ribosome structure will go toward providing insight into the mechanisms of eukaryotic translational regulation. Nevertheless, this information will help to understand prokaryotic initiation, and at least provide a starting point for interpreting the emerging structures of eukaryotic ribosomes. Most of the steps of protein synthesis appear to be based on RNA, including the many interactions between mRNA, tRNA, and rRNA that occur during the elongation phase. The roles of the proteins, such as the elongation factors and ribosomal proteins, may be to refine underlying RNA-based mechanisms, optimizing the speed and accuracy of translation. Translational initiation, at least in part, is therefore likely to involve modulation of RNA-based processes by proteins such as the initiation factors. We are beginning to understand how some of these processes work, from several decades of biochemical and genetic studies combined with the more recent...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"28 1","pages":"41-58"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87633535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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