Circular RNAs (circRNAs) are closed RNA loops present in humans and other organisms. Various circRNAs have an essential role in diseases, including cancer. Cells can release circRNAs into the extracellular space of adjacent biofluids and can be present in extracellular vesicles. Due to their circular nature, extracellular circRNAs (excircRNAs) are more stable than their linear counterparts and are abundant in many biofluids, such as blood plasma and urine. circRNAs' link with disease suggests their extracellular counterparts have high biomarker potential. However, circRNAs and the extracellular space are challenging research domains, as they consist of complex biological systems plagued with nomenclature issues and a wide variety of protocols with different advantages and disadvantages. Here, we summarize what is known about excircRNAs, the current challenges in the field, and what is needed to improve extracellular circRNA research.
{"title":"Current Understandings and Open Hypotheses on Extracellular Circular RNAs.","authors":"Jasper Verwilt, Marieke Vromman","doi":"10.1002/wrna.1872","DOIUrl":"10.1002/wrna.1872","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are closed RNA loops present in humans and other organisms. Various circRNAs have an essential role in diseases, including cancer. Cells can release circRNAs into the extracellular space of adjacent biofluids and can be present in extracellular vesicles. Due to their circular nature, extracellular circRNAs (excircRNAs) are more stable than their linear counterparts and are abundant in many biofluids, such as blood plasma and urine. circRNAs' link with disease suggests their extracellular counterparts have high biomarker potential. However, circRNAs and the extracellular space are challenging research domains, as they consist of complex biological systems plagued with nomenclature issues and a wide variety of protocols with different advantages and disadvantages. Here, we summarize what is known about excircRNAs, the current challenges in the field, and what is needed to improve extracellular circRNA research.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 6","pages":"e1872"},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Satya P Sharma, Mamta Chawla-Sarkar, Rajat Sandhir, Dipanjan Dutta
Influenza viruses (types A, B, C, and D) belong to the family orthomyxoviridae. Out of all the influenza types, influenza A virus (IAV) causes human pandemic outbreaks. Its pandemic potential is predominantly attributed to the genetic reassortment favored by a broad spectrum of host species that could lead to an antigenic shift along with a high rate of mutations in its genome, presenting a possibility of subtypes with heightened pathogenesis and virulence in humans (antigenic drift). In addition to antigenic shift and drift, there are several other inherent properties of its viral RNA species (vRNA, vmRNA, and cRNA) that significantly contribute to the success of specific stages of viral infection. In this review, we compile the key features of IAV RNA, such as sequence motifs and secondary structures, their functional significance in the infection cycle, and their overall impact on the virus's adaptive and evolutionary fitness. Because many of these motifs and folds are conserved, we also assess the existing antiviral approaches focused on targeting IAV RNA. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease.
{"title":"Decoding the role of RNA sequences and their interactions in influenza A virus infection and adaptation.","authors":"Satya P Sharma, Mamta Chawla-Sarkar, Rajat Sandhir, Dipanjan Dutta","doi":"10.1002/wrna.1871","DOIUrl":"https://doi.org/10.1002/wrna.1871","url":null,"abstract":"<p><p>Influenza viruses (types A, B, C, and D) belong to the family orthomyxoviridae. Out of all the influenza types, influenza A virus (IAV) causes human pandemic outbreaks. Its pandemic potential is predominantly attributed to the genetic reassortment favored by a broad spectrum of host species that could lead to an antigenic shift along with a high rate of mutations in its genome, presenting a possibility of subtypes with heightened pathogenesis and virulence in humans (antigenic drift). In addition to antigenic shift and drift, there are several other inherent properties of its viral RNA species (vRNA, vmRNA, and cRNA) that significantly contribute to the success of specific stages of viral infection. In this review, we compile the key features of IAV RNA, such as sequence motifs and secondary structures, their functional significance in the infection cycle, and their overall impact on the virus's adaptive and evolutionary fitness. Because many of these motifs and folds are conserved, we also assess the existing antiviral approaches focused on targeting IAV RNA. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 6","pages":"e1871"},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ribonucleic acid (RNA) undergoes dynamic changes in its structure and function under various intracellular and extracellular conditions over time. However, there is a lack of research on the concept of the RNA age to describe its diverse fates. This study proposes a definition of RNA age to address this issue. RNA age was defined as a sequence of numbers wherein the elements in the sequence were the nucleotide ages of the ribonucleotide residues in the RNA. Mean nucleotide age was used to represent RNA age. This definition describes the temporal properties of RNAs that have undergone diverse life histories and reflects the dynamic state of each ribonucleotide residue, which can be expressed mathematically. Notably, events (including base insertions, base deletions, and base substitutions) are likely to cause RNA to become younger or older when using mean nucleotide ages to represent the RNA age. Although information, including the presence of added markers in RNA, chemical modification structure of the RNA, and the excision of introns in the mRNA in cells, may provide a basis for identifying RNA age, little is known about determining the RNA age of extracellular RNA in the wild. Nonetheless, we believe that RNA age has an important relationship with the diverse biological properties of RNA under intracellular and extracellular conditions. Therefore, our proposed definition of RNA age offers new perspectives for studying dynamic changes in RNA function, RNA aging, ancient RNA, environmental RNA, and the ages of other biomolecules.
{"title":"The Definition of RNA Age Related to RNA Sequence Changes.","authors":"Zhongneng Xu, Shuichi Asakawa","doi":"10.1002/wrna.1876","DOIUrl":"https://doi.org/10.1002/wrna.1876","url":null,"abstract":"<p><p>Ribonucleic acid (RNA) undergoes dynamic changes in its structure and function under various intracellular and extracellular conditions over time. However, there is a lack of research on the concept of the RNA age to describe its diverse fates. This study proposes a definition of RNA age to address this issue. RNA age was defined as a sequence of numbers wherein the elements in the sequence were the nucleotide ages of the ribonucleotide residues in the RNA. Mean nucleotide age was used to represent RNA age. This definition describes the temporal properties of RNAs that have undergone diverse life histories and reflects the dynamic state of each ribonucleotide residue, which can be expressed mathematically. Notably, events (including base insertions, base deletions, and base substitutions) are likely to cause RNA to become younger or older when using mean nucleotide ages to represent the RNA age. Although information, including the presence of added markers in RNA, chemical modification structure of the RNA, and the excision of introns in the mRNA in cells, may provide a basis for identifying RNA age, little is known about determining the RNA age of extracellular RNA in the wild. Nonetheless, we believe that RNA age has an important relationship with the diverse biological properties of RNA under intracellular and extracellular conditions. Therefore, our proposed definition of RNA age offers new perspectives for studying dynamic changes in RNA function, RNA aging, ancient RNA, environmental RNA, and the ages of other biomolecules.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 6","pages":"e1876"},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolina Mathias, Ana Carolina Rodrigues, Suelen Cristina Soares Baal, Alexandre Luiz Korte de Azevedo, Vanessa Nascimento Kozak, Leticia Ferreira Alves, Jaqueline Carvalho de Oliveira, Sonia Guil, Daniela Fiori Gradia
Cellular compartmentalization, achieved through membrane-based compartments, is a fundamental aspect of cell biology that contributes to the evolutionary success of cells. While organelles have traditionally been the focus of research, membrane-less organelles (MLOs) are emerging as critical players, exhibiting distinct morphological features and unique molecular compositions. Recent research highlights the pivotal role of long noncoding RNAs (lncRNAs) in MLOs and their involvement in various cellular processes across different organisms. In the context of cancer, dysregulation of MLO formation, influenced by altered lncRNA expression, impacts chromatin organization, oncogenic transcription, signaling pathways, and telomere lengthening. This review synthesizes the current understanding of lncRNA composition within MLOs, delineating their functions and exploring how their dysregulation contributes to human cancers. Environmental challenges in tumorigenesis, such as nutrient deprivation and hypoxia, induce stress granules, promoting cancer cell survival and progression. Advancements in biochemical techniques, particularly single RNA imaging methods, offer valuable tools for studying RNA functions within live cells. However, detecting low-abundance lncRNAs remains challenging due to their limited expression levels. The correlation between lncRNA expression and pathological conditions, particularly cancer, should be explored, emphasizing the importance of single-cell studies for precise biomarker identification and the development of personalized therapeutic strategies. This article is categorized under: RNA Export and Localization > RNA Localization RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
{"title":"The landscape of lncRNAs in cell granules: Insights into their significance in cancer.","authors":"Carolina Mathias, Ana Carolina Rodrigues, Suelen Cristina Soares Baal, Alexandre Luiz Korte de Azevedo, Vanessa Nascimento Kozak, Leticia Ferreira Alves, Jaqueline Carvalho de Oliveira, Sonia Guil, Daniela Fiori Gradia","doi":"10.1002/wrna.1870","DOIUrl":"https://doi.org/10.1002/wrna.1870","url":null,"abstract":"<p><p>Cellular compartmentalization, achieved through membrane-based compartments, is a fundamental aspect of cell biology that contributes to the evolutionary success of cells. While organelles have traditionally been the focus of research, membrane-less organelles (MLOs) are emerging as critical players, exhibiting distinct morphological features and unique molecular compositions. Recent research highlights the pivotal role of long noncoding RNAs (lncRNAs) in MLOs and their involvement in various cellular processes across different organisms. In the context of cancer, dysregulation of MLO formation, influenced by altered lncRNA expression, impacts chromatin organization, oncogenic transcription, signaling pathways, and telomere lengthening. This review synthesizes the current understanding of lncRNA composition within MLOs, delineating their functions and exploring how their dysregulation contributes to human cancers. Environmental challenges in tumorigenesis, such as nutrient deprivation and hypoxia, induce stress granules, promoting cancer cell survival and progression. Advancements in biochemical techniques, particularly single RNA imaging methods, offer valuable tools for studying RNA functions within live cells. However, detecting low-abundance lncRNAs remains challenging due to their limited expression levels. The correlation between lncRNA expression and pathological conditions, particularly cancer, should be explored, emphasizing the importance of single-cell studies for precise biomarker identification and the development of personalized therapeutic strategies. This article is categorized under: RNA Export and Localization > RNA Localization RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 5","pages":"e1870"},"PeriodicalIF":6.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robert A Crawford, Matthew Eastham, Martin R Pool, Mark P Ashe
The mechanics of how proteins are generated from mRNA is increasingly well understood. However, much less is known about how protein production is coordinated and orchestrated within the crowded intracellular environment, especially in eukaryotic cells. Recent studies suggest that localized sites exist for the coordinated production of specific proteins. These sites have been termed "translation factories" and roles in protein complex formation, protein localization, inheritance, and translation regulation have been postulated. In this article, we review the evidence supporting the translation of mRNA at these sites, the details of their mechanism of formation, and their likely functional significance. Finally, we consider the key uncertainties regarding these elusive structures in cells. This article is categorized under: Translation Translation > Mechanisms RNA Export and Localization > RNA Localization Translation > Regulation.
{"title":"Orchestrated centers for the production of proteins or \"translation factories\".","authors":"Robert A Crawford, Matthew Eastham, Martin R Pool, Mark P Ashe","doi":"10.1002/wrna.1867","DOIUrl":"https://doi.org/10.1002/wrna.1867","url":null,"abstract":"<p><p>The mechanics of how proteins are generated from mRNA is increasingly well understood. However, much less is known about how protein production is coordinated and orchestrated within the crowded intracellular environment, especially in eukaryotic cells. Recent studies suggest that localized sites exist for the coordinated production of specific proteins. These sites have been termed \"translation factories\" and roles in protein complex formation, protein localization, inheritance, and translation regulation have been postulated. In this article, we review the evidence supporting the translation of mRNA at these sites, the details of their mechanism of formation, and their likely functional significance. Finally, we consider the key uncertainties regarding these elusive structures in cells. This article is categorized under: Translation Translation > Mechanisms RNA Export and Localization > RNA Localization Translation > Regulation.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 4","pages":"e1867"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pericentromeric heterochromatin is mainly composed of satellite DNA sequences. Although being historically associated with transcriptional repression, some pericentromeric satellite DNA sequences are transcribed. The transcription events of pericentromeric satellite sequences occur in highly flexible biological contexts. Hence, the apparent randomness of pericentromeric satellite transcription incites the discussion about the attribution of biological functions. However, pericentromeric satellite RNAs have clear roles in the organization of nuclear structure. Silencing pericentromeric heterochromatin depends on pericentromeric satellite RNAs, that, in a feedback mechanism, contribute to the repression of pericentromeric heterochromatin. Moreover, pericentromeric satellite RNAs can also act as scaffolding molecules in condensate subnuclear structures (e.g., nuclear stress bodies). Since the formation/dissociation of nuclear condensates provides cell adaptability, pericentromeric satellite RNAs can be an epigenetic platform for regulating (sub)nuclear structure. We review current knowledge about pericentromeric satellite RNAs that, irrespective of the meaning of biological function, should be functionally addressed in regular and disease settings. This article is categorized under: RNA Methods > RNA Analyses in Cells RNA in Disease and Development > RNA in Disease.
近染色质异染色质主要由卫星 DNA 序列组成。尽管卫星 DNA 序列在历史上与转录抑制有关,但有些中心染色质周围的卫星 DNA 序列也会被转录。中心周卫星序列的转录事件发生在高度灵活的生物环境中。因此,中心染色体周围卫星转录的明显随机性引发了有关生物功能归属的讨论。然而,近中心染色质卫星 RNA 在核结构的组织中具有明确的作用。沉默周染色质异染色质依赖于周染色质卫星 RNA,后者在反馈机制中有助于抑制周染色质异染色质。此外,围中心染色质卫星 RNA 还可以在凝聚的亚核结构(如核应激体)中充当支架分子。由于核凝聚体的形成/解离提供了细胞的适应性,因此包心染色质卫星 RNA 可以成为调节(亚)核结构的表观遗传平台。我们回顾了目前有关核周卫星 RNA 的知识,无论其生物学功能的意义如何,都应在常规和疾病环境中加以功能性处理。本文归类于RNA 方法 > 细胞中的 RNA 分析 疾病和发育中的 RNA > 疾病中的 RNA。
{"title":"Pericentromeric satellite RNAs as flexible protein partners in the regulation of nuclear structure.","authors":"Mariana Lopes, Sandra Louzada, Margarida Gama-Carvalho, Raquel Chaves","doi":"10.1002/wrna.1868","DOIUrl":"https://doi.org/10.1002/wrna.1868","url":null,"abstract":"<p><p>Pericentromeric heterochromatin is mainly composed of satellite DNA sequences. Although being historically associated with transcriptional repression, some pericentromeric satellite DNA sequences are transcribed. The transcription events of pericentromeric satellite sequences occur in highly flexible biological contexts. Hence, the apparent randomness of pericentromeric satellite transcription incites the discussion about the attribution of biological functions. However, pericentromeric satellite RNAs have clear roles in the organization of nuclear structure. Silencing pericentromeric heterochromatin depends on pericentromeric satellite RNAs, that, in a feedback mechanism, contribute to the repression of pericentromeric heterochromatin. Moreover, pericentromeric satellite RNAs can also act as scaffolding molecules in condensate subnuclear structures (e.g., nuclear stress bodies). Since the formation/dissociation of nuclear condensates provides cell adaptability, pericentromeric satellite RNAs can be an epigenetic platform for regulating (sub)nuclear structure. We review current knowledge about pericentromeric satellite RNAs that, irrespective of the meaning of biological function, should be functionally addressed in regular and disease settings. This article is categorized under: RNA Methods > RNA Analyses in Cells RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 4","pages":"e1868"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA structure is crucial to a wide range of cellular processes. The intimate relationship between macromolecular structure and function necessitates the determination of high-resolution structures of functional RNA molecules. X-ray crystallography is the predominant technique used for macromolecular structure determination; however, solving RNA structures has been more challenging than their protein counterparts, as reflected in their poor representation in the Protein Data Bank (<1%). Antibody-assisted RNA crystallography is a relatively new technique that promises to accelerate RNA structure determination by employing synthetic antibodies (Fabs) as crystallization chaperones that are specifically raised against target RNAs. Antibody chaperones facilitate the formation of ordered crystal lattices by minimizing RNA flexibility and replacing unfavorable RNA-RNA contacts with contacts between chaperone molecules. Atomic coordinates of these antibody fragments can also be used as search models to obtain phase information during structure determination. Antibody-assisted RNA crystallography has enabled the structure determination of 15 unique RNA targets, including 11 in the last 6 years. In this review, I cover the historical development of antibody fragments as crystallization chaperones and their application to diverse RNA targets. I discuss how the first structures of antibody-RNA complexes informed the design of second-generation antibodies and led to the development of portable crystallization modules that have greatly reduced the uncertainties associated with RNA crystallography. Finally, I outline unexplored avenues that can increase the impact of this technology in structural biology research and discuss potential applications of antibodies as affinity reagents for interrogating RNA biology outside of their use in crystallography. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
RNA 结构对多种细胞过程至关重要。由于大分子结构与功能之间的密切关系,有必要确定功能 RNA 分子的高分辨率结构。X 射线晶体学是用于确定大分子结构的主要技术;然而,解决 RNA 结构问题比解决蛋白质结构问题更具挑战性,这反映在它们在蛋白质数据库(RNA Structure, Dynamics and Chemistry RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes)中的代表性较差。
{"title":"Synthetic antibodies for accelerated RNA crystallography.","authors":"Saurja DasGupta","doi":"10.1002/wrna.1869","DOIUrl":"https://doi.org/10.1002/wrna.1869","url":null,"abstract":"<p><p>RNA structure is crucial to a wide range of cellular processes. The intimate relationship between macromolecular structure and function necessitates the determination of high-resolution structures of functional RNA molecules. X-ray crystallography is the predominant technique used for macromolecular structure determination; however, solving RNA structures has been more challenging than their protein counterparts, as reflected in their poor representation in the Protein Data Bank (<1%). Antibody-assisted RNA crystallography is a relatively new technique that promises to accelerate RNA structure determination by employing synthetic antibodies (Fabs) as crystallization chaperones that are specifically raised against target RNAs. Antibody chaperones facilitate the formation of ordered crystal lattices by minimizing RNA flexibility and replacing unfavorable RNA-RNA contacts with contacts between chaperone molecules. Atomic coordinates of these antibody fragments can also be used as search models to obtain phase information during structure determination. Antibody-assisted RNA crystallography has enabled the structure determination of 15 unique RNA targets, including 11 in the last 6 years. In this review, I cover the historical development of antibody fragments as crystallization chaperones and their application to diverse RNA targets. I discuss how the first structures of antibody-RNA complexes informed the design of second-generation antibodies and led to the development of portable crystallization modules that have greatly reduced the uncertainties associated with RNA crystallography. Finally, I outline unexplored avenues that can increase the impact of this technology in structural biology research and discuss potential applications of antibodies as affinity reagents for interrogating RNA biology outside of their use in crystallography. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 4","pages":"e1869"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subhadeep Das, Maria Paula Zea Rojas, Elizabeth J Tran
A considerable proportion of the eukaryotic genome undergoes transcription, leading to the generation of noncoding RNA molecules that lack protein-coding information and are not subjected to translation. These noncoding RNAs (ncRNAs) are well recognized to have essential roles in several biological processes. Long noncoding RNAs (lncRNAs) represent the most extensive category of ncRNAs found in the human genome. Much research has focused on investigating the roles of cis-acting lncRNAs in the regulation of specific target gene expression. In the majority of instances, the regulation of sense gene expression by its corresponding antisense pair occurs in a negative (discordant) manner, resulting in the suppression of the target genes. The notion that a negative correlation exists between sense and antisense pairings is, however, not universally valid. In fact, several recent studies have reported a positive relationship between corresponding cis antisense pairs within plants, budding yeast, and mammalian cancer cells. The positive (concordant) correlation between anti-sense and sense transcripts leads to an increase in the level of the sense transcript within the same genomic loci. In addition, mechanisms such as altering chromatin structure, the formation of R loops, and the recruitment of transcription factors can either enhance transcription or stabilize sense transcripts through their antisense pairs. The primary objective of this work is to provide a comprehensive understanding of both aspects of antisense regulation, specifically focusing on the positive correlation between sense and antisense transcripts in the context of eukaryotic gene expression, including its implications towards cancer progression. This article is categorized under: RNA Processing > 3' End Processing Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
{"title":"Novel insights on the positive correlation between sense and antisense pairs on gene expression.","authors":"Subhadeep Das, Maria Paula Zea Rojas, Elizabeth J Tran","doi":"10.1002/wrna.1864","DOIUrl":"10.1002/wrna.1864","url":null,"abstract":"<p><p>A considerable proportion of the eukaryotic genome undergoes transcription, leading to the generation of noncoding RNA molecules that lack protein-coding information and are not subjected to translation. These noncoding RNAs (ncRNAs) are well recognized to have essential roles in several biological processes. Long noncoding RNAs (lncRNAs) represent the most extensive category of ncRNAs found in the human genome. Much research has focused on investigating the roles of cis-acting lncRNAs in the regulation of specific target gene expression. In the majority of instances, the regulation of sense gene expression by its corresponding antisense pair occurs in a negative (discordant) manner, resulting in the suppression of the target genes. The notion that a negative correlation exists between sense and antisense pairings is, however, not universally valid. In fact, several recent studies have reported a positive relationship between corresponding cis antisense pairs within plants, budding yeast, and mammalian cancer cells. The positive (concordant) correlation between anti-sense and sense transcripts leads to an increase in the level of the sense transcript within the same genomic loci. In addition, mechanisms such as altering chromatin structure, the formation of R loops, and the recruitment of transcription factors can either enhance transcription or stabilize sense transcripts through their antisense pairs. The primary objective of this work is to provide a comprehensive understanding of both aspects of antisense regulation, specifically focusing on the positive correlation between sense and antisense transcripts in the context of eukaryotic gene expression, including its implications towards cancer progression. This article is categorized under: RNA Processing > 3' End Processing Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 4","pages":"e1864"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pre-mRNA splicing, the removal of introns and ligation of flanking exons, is a crucial step in eukaryotic gene expression. The spliceosome, a macromolecular complex made up of five small nuclear RNAs (snRNAs) and dozens of proteins, assembles on introns via a complex pathway before catalyzing the two transesterification reactions necessary for splicing. All of these steps have the potential to be highly regulated to ensure correct mRNA isoform production for proper cellular function. While Saccharomyces cerevisiae (yeast) has a limited set of intron-containing genes, many of these genes are highly expressed, resulting in a large number of transcripts in a cell being spliced. As a result, splicing regulation is of critical importance for yeast. Just as in humans, yeast splicing can be influenced by protein components of the splicing machinery, structures and properties of the pre-mRNA itself, or by the action of trans-acting factors. It is likely that further analysis of the mechanisms and pathways of splicing regulation in yeast can reveal general principles applicable to other eukaryotes. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.
{"title":"Mechanisms and regulation of spliceosome-mediated pre-mRNA splicing in Saccharomyces cerevisiae.","authors":"Katherine Anne Senn, Aaron A Hoskins","doi":"10.1002/wrna.1866","DOIUrl":"10.1002/wrna.1866","url":null,"abstract":"<p><p>Pre-mRNA splicing, the removal of introns and ligation of flanking exons, is a crucial step in eukaryotic gene expression. The spliceosome, a macromolecular complex made up of five small nuclear RNAs (snRNAs) and dozens of proteins, assembles on introns via a complex pathway before catalyzing the two transesterification reactions necessary for splicing. All of these steps have the potential to be highly regulated to ensure correct mRNA isoform production for proper cellular function. While Saccharomyces cerevisiae (yeast) has a limited set of intron-containing genes, many of these genes are highly expressed, resulting in a large number of transcripts in a cell being spliced. As a result, splicing regulation is of critical importance for yeast. Just as in humans, yeast splicing can be influenced by protein components of the splicing machinery, structures and properties of the pre-mRNA itself, or by the action of trans-acting factors. It is likely that further analysis of the mechanisms and pathways of splicing regulation in yeast can reveal general principles applicable to other eukaryotes. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 4","pages":"e1866"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renrui Chen, Pengxing Nie, Jing Wang, Guang-Zhong Wang
The brain is a complex computing system composed of a multitude of interacting neurons. The computational outputs of this system determine the behavior and perception of every individual. Each brain cell expresses thousands of genes that dictate the cell's function and physiological properties. Therefore, deciphering the molecular expression of each cell is of great significance for understanding its characteristics and role in brain function. Additionally, the positional information of each cell can provide crucial insights into their involvement in local brain circuits. In this review, we briefly overview the principles of single-cell RNA sequencing and spatial transcriptomics, the potential issues and challenges in their data processing, and their applications in brain research. We further outline several promising directions in neuroscience that could be integrated with single-cell RNA sequencing, including neurodevelopment, the identification of novel brain microstructures, cognition and behavior, neuronal cell positioning, molecules and cells related to advanced brain functions, sleep-wake cycles/circadian rhythms, and computational modeling of brain function. We believe that the deep integration of these directions with single-cell and spatial RNA sequencing can contribute significantly to understanding the roles of individual cells or cell types in these specific functions, thereby making important contributions to addressing critical questions in those fields. This article is categorized under: RNA Evolution and Genomics > Computational Analyses of RNA RNA in Disease and Development > RNA in Development RNA in Disease and Development > RNA in Disease.
{"title":"Deciphering brain cellular and behavioral mechanisms: Insights from single-cell and spatial RNA sequencing.","authors":"Renrui Chen, Pengxing Nie, Jing Wang, Guang-Zhong Wang","doi":"10.1002/wrna.1865","DOIUrl":"https://doi.org/10.1002/wrna.1865","url":null,"abstract":"<p><p>The brain is a complex computing system composed of a multitude of interacting neurons. The computational outputs of this system determine the behavior and perception of every individual. Each brain cell expresses thousands of genes that dictate the cell's function and physiological properties. Therefore, deciphering the molecular expression of each cell is of great significance for understanding its characteristics and role in brain function. Additionally, the positional information of each cell can provide crucial insights into their involvement in local brain circuits. In this review, we briefly overview the principles of single-cell RNA sequencing and spatial transcriptomics, the potential issues and challenges in their data processing, and their applications in brain research. We further outline several promising directions in neuroscience that could be integrated with single-cell RNA sequencing, including neurodevelopment, the identification of novel brain microstructures, cognition and behavior, neuronal cell positioning, molecules and cells related to advanced brain functions, sleep-wake cycles/circadian rhythms, and computational modeling of brain function. We believe that the deep integration of these directions with single-cell and spatial RNA sequencing can contribute significantly to understanding the roles of individual cells or cell types in these specific functions, thereby making important contributions to addressing critical questions in those fields. This article is categorized under: RNA Evolution and Genomics > Computational Analyses of RNA RNA in Disease and Development > RNA in Development RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 4","pages":"e1865"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}