The precursor transfer RNAs (pre-tRNAs) require extensive processing to generate mature tRNAs possessing proper fold, structural stability, and functionality required to sustain cellular viability. The road to tRNA maturation follows an ordered process: 5'-processing, 3'-processing, modifications at specific sites, if any, and 3'-CCA addition before aminoacylation and recruitment to the cellular protein synthesis machinery. Ribonuclease P (RNase P) is a universally conserved endonuclease in all domains of life, performing the hydrolysis of pre-tRNA sequences at the 5' end by the removal of phosphodiester linkages between nucleotides at position -1 and +1. Except for an archaeal species: Nanoarchaeum equitans where tRNAs are transcribed from leaderless-position +1, RNase P is indispensable for life and displays fundamental variations in terms of enzyme subunit composition, mechanism of substrate recognition and active site architecture, utilizing in all cases a two metal ion-mediated conserved catalytic reaction. While the canonical RNA-based ribonucleoprotein RNase P has been well-known to occur in bacteria, archaea, and eukaryotes, the occurrence of RNA-free protein-only RNase P in eukaryotes and RNA-free homologs of Aquifex RNase P in prokaryotes has been discovered more recently. This review aims to provide a comprehensive overview of structural diversity displayed by various RNA-based and RNA-free RNase P holoenzymes towards harnessing critical RNA-protein and protein-protein interactions in achieving conserved pre-tRNA processing functionality. Furthermore, alternate roles and functional interchangeability of RNase P are discussed in the context of its employability in several clinical and biotechnological applications. This article is categorized under: RNA Processing > tRNA Processing RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
{"title":"Multiple structural flavors of RNase P in precursor tRNA processing.","authors":"Sagar Sridhara","doi":"10.1002/wrna.1835","DOIUrl":"10.1002/wrna.1835","url":null,"abstract":"<p><p>The precursor transfer RNAs (pre-tRNAs) require extensive processing to generate mature tRNAs possessing proper fold, structural stability, and functionality required to sustain cellular viability. The road to tRNA maturation follows an ordered process: 5'-processing, 3'-processing, modifications at specific sites, if any, and 3'-CCA addition before aminoacylation and recruitment to the cellular protein synthesis machinery. Ribonuclease P (RNase P) is a universally conserved endonuclease in all domains of life, performing the hydrolysis of pre-tRNA sequences at the 5' end by the removal of phosphodiester linkages between nucleotides at position -1 and +1. Except for an archaeal species: Nanoarchaeum equitans where tRNAs are transcribed from leaderless-position +1, RNase P is indispensable for life and displays fundamental variations in terms of enzyme subunit composition, mechanism of substrate recognition and active site architecture, utilizing in all cases a two metal ion-mediated conserved catalytic reaction. While the canonical RNA-based ribonucleoprotein RNase P has been well-known to occur in bacteria, archaea, and eukaryotes, the occurrence of RNA-free protein-only RNase P in eukaryotes and RNA-free homologs of Aquifex RNase P in prokaryotes has been discovered more recently. This review aims to provide a comprehensive overview of structural diversity displayed by various RNA-based and RNA-free RNase P holoenzymes towards harnessing critical RNA-protein and protein-protein interactions in achieving conserved pre-tRNA processing functionality. Furthermore, alternate roles and functional interchangeability of RNase P are discussed in the context of its employability in several clinical and biotechnological applications. This article is categorized under: RNA Processing > tRNA Processing RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120813","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}
Spatially resolved transcriptomics has been dramatically transforming biological and medical research in various fields. It enables transcriptome profiling at single-cell, multi-cellular, or sub-cellular resolution, while retaining the information of geometric localizations of cells in complex tissues. The coupling of cell spatial information and its molecular characteristics generates a novel multi-modal high-throughput data source, which poses new challenges for the development of analytical methods for data-mining. Spatial transcriptomic data are often highly complex, noisy, and biased, presenting a series of difficulties, many unresolved, for data analysis and generation of biological insights. In addition, to keep pace with the ever-evolving spatial transcriptomic experimental technologies, the existing analytical theories and tools need to be updated and reformed accordingly. In this review, we provide an overview and discussion of the current computational approaches for mining of spatial transcriptomics data. Future directions and perspectives of methodology design are proposed to stimulate further discussions and advances in new analytical models and algorithms. This article is categorized under: RNA Methods > RNA Analyses in Cells RNA Evolution and Genomics > Computational Analyses of RNA RNA Export and Localization > RNA Localization.
{"title":"Navigating the landscapes of spatial transcriptomics: How computational methods guide the way.","authors":"Runze Li, Xu Chen, Xuerui Yang","doi":"10.1002/wrna.1839","DOIUrl":"10.1002/wrna.1839","url":null,"abstract":"<p><p>Spatially resolved transcriptomics has been dramatically transforming biological and medical research in various fields. It enables transcriptome profiling at single-cell, multi-cellular, or sub-cellular resolution, while retaining the information of geometric localizations of cells in complex tissues. The coupling of cell spatial information and its molecular characteristics generates a novel multi-modal high-throughput data source, which poses new challenges for the development of analytical methods for data-mining. Spatial transcriptomic data are often highly complex, noisy, and biased, presenting a series of difficulties, many unresolved, for data analysis and generation of biological insights. In addition, to keep pace with the ever-evolving spatial transcriptomic experimental technologies, the existing analytical theories and tools need to be updated and reformed accordingly. In this review, we provide an overview and discussion of the current computational approaches for mining of spatial transcriptomics data. Future directions and perspectives of methodology design are proposed to stimulate further discussions and advances in new analytical models and algorithms. This article is categorized under: RNA Methods > RNA Analyses in Cells RNA Evolution and Genomics > Computational Analyses of RNA RNA Export and Localization > RNA Localization.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289106","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}
{"title":"Correction to \"Poly(A) tale: From A to A; RNA polyadenylation in prokaryotes and eukaryotes\".","authors":"","doi":"10.1002/wrna.1846","DOIUrl":"10.1002/wrna.1846","url":null,"abstract":"","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858141","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}
Thomas Balan, Leticia Koch Lerner, Daniel Holoch, Sandra Duharcourt
Transposable elements and other repeats are repressed by small-RNA-guided histone modifications in fungi, plants and animals. The specificity of silencing is achieved through base-pairing of small RNAs corresponding to the these genomic loci to nascent noncoding RNAs, which allows the recruitment of histone methyltransferases that methylate histone H3 on lysine 9. Self-reinforcing feedback loops enhance small RNA production and ensure robust and heritable repression. In the unicellular ciliate Paramecium tetraurelia, small-RNA-guided histone modifications lead to the elimination of transposable elements and their remnants, a definitive form of repression. In this organism, germline and somatic functions are separated within two types of nuclei with different genomes. At each sexual cycle, development of the somatic genome is accompanied by the reproducible removal of approximately a third of the germline genome. Instead of recruiting a H3K9 methyltransferase, small RNAs corresponding to eliminated sequences tether Polycomb Repressive Complex 2, which in ciliates has the unique property of catalyzing both lysine 9 and lysine 27 trimethylation of histone H3. These histone modifications that are crucial for the elimination of transposable elements are thought to guide the endonuclease complex, which triggers double-strand breaks at these specific genomic loci. The comparison between ciliates and other eukaryotes underscores the importance of investigating small-RNAs-directed chromatin silencing in a diverse range of organisms. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action.
{"title":"Small-RNA-guided histone modifications and somatic genome elimination in ciliates.","authors":"Thomas Balan, Leticia Koch Lerner, Daniel Holoch, Sandra Duharcourt","doi":"10.1002/wrna.1848","DOIUrl":"10.1002/wrna.1848","url":null,"abstract":"<p><p>Transposable elements and other repeats are repressed by small-RNA-guided histone modifications in fungi, plants and animals. The specificity of silencing is achieved through base-pairing of small RNAs corresponding to the these genomic loci to nascent noncoding RNAs, which allows the recruitment of histone methyltransferases that methylate histone H3 on lysine 9. Self-reinforcing feedback loops enhance small RNA production and ensure robust and heritable repression. In the unicellular ciliate Paramecium tetraurelia, small-RNA-guided histone modifications lead to the elimination of transposable elements and their remnants, a definitive form of repression. In this organism, germline and somatic functions are separated within two types of nuclei with different genomes. At each sexual cycle, development of the somatic genome is accompanied by the reproducible removal of approximately a third of the germline genome. Instead of recruiting a H3K9 methyltransferase, small RNAs corresponding to eliminated sequences tether Polycomb Repressive Complex 2, which in ciliates has the unique property of catalyzing both lysine 9 and lysine 27 trimethylation of histone H3. These histone modifications that are crucial for the elimination of transposable elements are thought to guide the endonuclease complex, which triggers double-strand breaks at these specific genomic loci. The comparison between ciliates and other eukaryotes underscores the importance of investigating small-RNAs-directed chromatin silencing in a diverse range of organisms. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854687","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}
Spatial transcriptomics (ST) is featured by high-throughput gene expression profiling within their native cell and tissue context, offering a means to investigate gene regulatory networks in tissue microenvironment. In situ sequencing (ISS) is an imaging-based ST technology that simultaneously detects hundreds to thousands of genes at subcellular resolution. As a highly reproducible and robust technique, ISS has been widely adapted and undergone a series of technical iterations. As the interest in ISS-based spatial transcriptomic analysis grows, scalable and integrated data analysis workflows are needed to facilitate the applications of ISS in different research fields. This review presents the state-of-the-art bioinformatic toolkits for ISS data analysis, which covers the upstream and downstream analysis workflows, including image analysis, cell segmentation, clustering, functional enrichment, detection of spatially variable genes and cell clusters, spatial cell-cell interactions, and trajectory inference. To assist the community in choosing the right tools for their research, the application of each tool and its compatibility with ISS data are reviewed in detailed. Finally, future perspectives and challenges concerning how to integrate heterogeneous tools into a user-friendly analysis pipeline are discussed. This article is categorized under: RNA Methods > RNA Analyses In Vitro and In Silico.
空间转录组学(ST)的特点是在原生细胞和组织背景下进行高通量基因表达谱分析,为研究组织微环境中的基因调控网络提供了一种手段。原位测序(ISS)是一种基于成像的空间转录组学技术,可同时检测亚细胞分辨率的数百至数千个基因。作为一种具有高度可重复性和稳健性的技术,原位测序已被广泛采用并经历了一系列技术迭代。随着人们对基于 ISS 的空间转录组分析的兴趣与日俱增,需要可扩展的集成数据分析工作流程来促进 ISS 在不同研究领域的应用。本综述介绍了最先进的 ISS 数据分析生物信息学工具包,涵盖了上游和下游分析工作流程,包括图像分析、细胞分割、聚类、功能富集、空间可变基因和细胞簇检测、空间细胞-细胞相互作用以及轨迹推断。为了帮助社区为其研究选择合适的工具,我们详细介绍了每种工具的应用及其与 ISS 数据的兼容性。最后,还讨论了如何将异构工具整合到用户友好的分析管道中的未来展望和挑战。本文归类于RNA 方法 > 体外和硅学 RNA 分析。
{"title":"Spatial analysis toolkits for RNA in situ sequencing.","authors":"Jiayu Chen, Rongqin Ke","doi":"10.1002/wrna.1842","DOIUrl":"10.1002/wrna.1842","url":null,"abstract":"<p><p>Spatial transcriptomics (ST) is featured by high-throughput gene expression profiling within their native cell and tissue context, offering a means to investigate gene regulatory networks in tissue microenvironment. In situ sequencing (ISS) is an imaging-based ST technology that simultaneously detects hundreds to thousands of genes at subcellular resolution. As a highly reproducible and robust technique, ISS has been widely adapted and undergone a series of technical iterations. As the interest in ISS-based spatial transcriptomic analysis grows, scalable and integrated data analysis workflows are needed to facilitate the applications of ISS in different research fields. This review presents the state-of-the-art bioinformatic toolkits for ISS data analysis, which covers the upstream and downstream analysis workflows, including image analysis, cell segmentation, clustering, functional enrichment, detection of spatially variable genes and cell clusters, spatial cell-cell interactions, and trajectory inference. To assist the community in choosing the right tools for their research, the application of each tool and its compatibility with ISS data are reviewed in detailed. Finally, future perspectives and challenges concerning how to integrate heterogeneous tools into a user-friendly analysis pipeline are discussed. This article is categorized under: RNA Methods > RNA Analyses In Vitro and In Silico.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854688","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}
A rampant and urgent global health issue of the 21st century is the emergence and progression of fatty liver disease (FLD), including alcoholic fatty liver disease and the more heterogenous metabolism-associated (or non-alcoholic) fatty liver disease (MAFLD/NAFLD) phenotypes. These conditions manifest as disease spectra, progressing from benign hepatic steatosis to symptomatic steatohepatitis, cirrhosis, and, ultimately, hepatocellular carcinoma. With numerous intricately regulated molecular pathways implicated in its pathophysiology, recent data have emphasized the critical roles of RNA-binding proteins (RBPs) in the onset and development of FLD. They regulate gene transcription and post-transcriptional processes, including pre-mRNA splicing, capping, and polyadenylation, as well as mature mRNA transport, stability, and translation. RBP dysfunction at every point along the mRNA life cycle has been associated with altered lipid metabolism and cellular stress response, resulting in hepatic inflammation and fibrosis. Here, we discuss the current understanding of the role of RBPs in the post-transcriptional processes associated with FLD and highlight the possible and emerging therapeutic strategies leveraging RBP function for FLD treatment. This article is categorized under: RNA in Disease and Development > RNA in Disease.
{"title":"Emerging roles of RNA-binding proteins in fatty liver disease.","authors":"Oluwafolajimi Adesanya, Diptatanu Das, Auinash Kalsotra","doi":"10.1002/wrna.1840","DOIUrl":"10.1002/wrna.1840","url":null,"abstract":"<p><p>A rampant and urgent global health issue of the 21st century is the emergence and progression of fatty liver disease (FLD), including alcoholic fatty liver disease and the more heterogenous metabolism-associated (or non-alcoholic) fatty liver disease (MAFLD/NAFLD) phenotypes. These conditions manifest as disease spectra, progressing from benign hepatic steatosis to symptomatic steatohepatitis, cirrhosis, and, ultimately, hepatocellular carcinoma. With numerous intricately regulated molecular pathways implicated in its pathophysiology, recent data have emphasized the critical roles of RNA-binding proteins (RBPs) in the onset and development of FLD. They regulate gene transcription and post-transcriptional processes, including pre-mRNA splicing, capping, and polyadenylation, as well as mature mRNA transport, stability, and translation. RBP dysfunction at every point along the mRNA life cycle has been associated with altered lipid metabolism and cellular stress response, resulting in hepatic inflammation and fibrosis. Here, we discuss the current understanding of the role of RBPs in the post-transcriptional processes associated with FLD and highlight the possible and emerging therapeutic strategies leveraging RBP function for FLD treatment. This article is categorized under: RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858114","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}
Pub Date : 2024-01-01Epub Date: 2023-12-19DOI: 10.1002/wrna.1829
Jinghua Gu, Huake Cao, Xiaoli Chen, Xu Dong Zhang, Rick F Thorne, Xiaoying Liu
In recent years, m6A modifications in RNA transcripts have arisen as a hot topic in cancer research. Indeed, a number of independent studies have elaborated that the m6A modification impacts the behavior of tumor cells and tumor-infiltrating immune cells, altering tumor cell metabolism along with the differentiation and functional activity of immune cells. This review elaborates on the links between RNA m6A modifications, tumor cell metabolism, and immune cell behavior, discussing this topic from the viewpoint of reciprocal regulation through "RNA m6A-tumor cell metabolism-immune cell behavior" and "RNA m6A-immune cell behavior-tumor cell metabolism" axes. In addition, we discuss the various factors affecting RNA m6A modifications in the tumor microenvironment, particularly the effects of hypoxia associated with cancer cell metabolism along with immune cell-secreted cytokines. Our analysis proposes the conclusion that RNA m6A modifications support widespread interactions between tumor metabolism and tumor immunity. With the current viewpoint that long-term cancer control must tackle cancer cell malignant behavior while strengthening anti-tumor immunity, the recognition of RNA m6A modifications as a key factor provides a new direction for the targeted therapy of tumors. This article is categorized under: RNA Processing > RNA Editing and Modification RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.
近年来,RNA 转录本中的 m6A 修饰已成为癌症研究的热点话题。事实上,许多独立研究已经阐述了 m6A 修饰会影响肿瘤细胞和肿瘤浸润免疫细胞的行为,改变肿瘤细胞的新陈代谢以及免疫细胞的分化和功能活性。本综述阐述了 RNA m6A 修饰、肿瘤细胞代谢和免疫细胞行为之间的联系,从 "RNA m6A-肿瘤细胞代谢-免疫细胞行为 "和 "RNA m6A-免疫细胞行为-肿瘤细胞代谢 "这两个轴相互调控的角度讨论了这一主题。此外,我们还讨论了影响肿瘤微环境中 RNA m6A 修饰的各种因素,特别是与癌细胞代谢相关的缺氧和免疫细胞分泌的细胞因子的影响。我们的分析得出的结论是,RNA m6A修饰支持肿瘤代谢与肿瘤免疫之间的广泛相互作用。目前的观点认为,长期的癌症控制必须在加强抗肿瘤免疫力的同时解决癌细胞的恶性行为,RNA m6A修饰作为一个关键因素的认识为肿瘤的靶向治疗提供了一个新的方向。本文归类于RNA Processing > RNA Editing and Modification RNA in Disease and Development > RNA in Disease RNA与蛋白质和其他分子的相互作用 > Protein-RNA Interactions:功能影响。
{"title":"RNA m6A modifications regulate crosstalk between tumor metabolism and immunity.","authors":"Jinghua Gu, Huake Cao, Xiaoli Chen, Xu Dong Zhang, Rick F Thorne, Xiaoying Liu","doi":"10.1002/wrna.1829","DOIUrl":"10.1002/wrna.1829","url":null,"abstract":"<p><p>In recent years, m6A modifications in RNA transcripts have arisen as a hot topic in cancer research. Indeed, a number of independent studies have elaborated that the m6A modification impacts the behavior of tumor cells and tumor-infiltrating immune cells, altering tumor cell metabolism along with the differentiation and functional activity of immune cells. This review elaborates on the links between RNA m6A modifications, tumor cell metabolism, and immune cell behavior, discussing this topic from the viewpoint of reciprocal regulation through \"RNA m6A-tumor cell metabolism-immune cell behavior\" and \"RNA m6A-immune cell behavior-tumor cell metabolism\" axes. In addition, we discuss the various factors affecting RNA m6A modifications in the tumor microenvironment, particularly the effects of hypoxia associated with cancer cell metabolism along with immune cell-secreted cytokines. Our analysis proposes the conclusion that RNA m6A modifications support widespread interactions between tumor metabolism and tumor immunity. With the current viewpoint that long-term cancer control must tackle cancer cell malignant behavior while strengthening anti-tumor immunity, the recognition of RNA m6A modifications as a key factor provides a new direction for the targeted therapy of tumors. This article is categorized under: RNA Processing > RNA Editing and Modification RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804646","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}
Sebastian Benjamin Schnoor, Peter Neubauer, Matthias Gimpel
Dual-function sRNAs refer to a small subgroup of small regulatory RNAs that merges base-pairing properties of antisense RNAs with peptide-encoding properties of mRNA. Both functions can be part of either same or in another metabolic pathway. Here, we want to update the knowledge of to the already known dual-function sRNAs and review the six new sRNAs found since 2017 regarding their structure, functional mechanisms, evolutionary conservation, and role in the regulation of distinct biological/physiological processes. The increasing identification of dual-function sRNAs through bioinformatics approaches, RNomics and RNA-sequencing and the associated increase in regulatory understanding will likely continue to increase at the same rate in the future. This may improve our understanding of the physiology, virulence and resistance of bacteria, as well as enable their use in technical applications. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
{"title":"Recent insights into the world of dual-function bacterial sRNAs.","authors":"Sebastian Benjamin Schnoor, Peter Neubauer, Matthias Gimpel","doi":"10.1002/wrna.1824","DOIUrl":"https://doi.org/10.1002/wrna.1824","url":null,"abstract":"<p><p>Dual-function sRNAs refer to a small subgroup of small regulatory RNAs that merges base-pairing properties of antisense RNAs with peptide-encoding properties of mRNA. Both functions can be part of either same or in another metabolic pathway. Here, we want to update the knowledge of to the already known dual-function sRNAs and review the six new sRNAs found since 2017 regarding their structure, functional mechanisms, evolutionary conservation, and role in the regulation of distinct biological/physiological processes. The increasing identification of dual-function sRNAs through bioinformatics approaches, RNomics and RNA-sequencing and the associated increase in regulatory understanding will likely continue to increase at the same rate in the future. This may improve our understanding of the physiology, virulence and resistance of bacteria, as well as enable their use in technical applications. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138471023","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}
Exposure to stress activates a well-orchestrated set of changes in gene expression programs that allow the cell to cope with and adapt to the stress, or undergo programmed cell death. RNA-protein interactions, mediating all aspects of post-transcriptional regulation of gene expression, play crucial roles in cellular stress responses. RNA-binding proteins (RBPs), which interact with sequence/structural elements in RNAs to control the steps of RNA metabolism, have therefore emerged as central regulators of post-transcriptional responses to stress. Following exposure to a variety of stresses, the dynamic alterations in the RNA-protein interactome enable cells to respond to intracellular or extracellular perturbations by causing changes in mRNA splicing, polyadenylation, stability, translation, and localization. As RBPs play a central role in determining the cellular proteome both qualitatively and quantitatively, it has become increasingly evident that their abundance, availability, and functions are also highly regulated in response to stress. Exposure to stress initiates a series of signaling cascades that converge on post-translational modifications (PTMs) of RBPs, resulting in changes in their subcellular localization, association with stress granules, extracellular export, proteasomal degradation, and RNA-binding activities. These alterations in the fate and function of RBPs directly impact their post-transcriptional regulatory roles in cells under stress. Adopting the ubiquitous RBP HuR as a prototype, three scenarios illustrating the changes in nuclear-cytoplasmic localization, RNA-binding activity, export and degradation of HuR in response to inflammation, genotoxic stress, and heat shock depict the complex and interlinked regulatory mechanisms that control the fate and functions of RBPs under stress. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.
{"title":"Fates and functions of RNA-binding proteins under stress.","authors":"Binita Goswami, Sharanya Nag, Partho Sarothi Ray","doi":"10.1002/wrna.1825","DOIUrl":"10.1002/wrna.1825","url":null,"abstract":"<p><p>Exposure to stress activates a well-orchestrated set of changes in gene expression programs that allow the cell to cope with and adapt to the stress, or undergo programmed cell death. RNA-protein interactions, mediating all aspects of post-transcriptional regulation of gene expression, play crucial roles in cellular stress responses. RNA-binding proteins (RBPs), which interact with sequence/structural elements in RNAs to control the steps of RNA metabolism, have therefore emerged as central regulators of post-transcriptional responses to stress. Following exposure to a variety of stresses, the dynamic alterations in the RNA-protein interactome enable cells to respond to intracellular or extracellular perturbations by causing changes in mRNA splicing, polyadenylation, stability, translation, and localization. As RBPs play a central role in determining the cellular proteome both qualitatively and quantitatively, it has become increasingly evident that their abundance, availability, and functions are also highly regulated in response to stress. Exposure to stress initiates a series of signaling cascades that converge on post-translational modifications (PTMs) of RBPs, resulting in changes in their subcellular localization, association with stress granules, extracellular export, proteasomal degradation, and RNA-binding activities. These alterations in the fate and function of RBPs directly impact their post-transcriptional regulatory roles in cells under stress. Adopting the ubiquitous RBP HuR as a prototype, three scenarios illustrating the changes in nuclear-cytoplasmic localization, RNA-binding activity, export and degradation of HuR in response to inflammation, genotoxic stress, and heat shock depict the complex and interlinked regulatory mechanisms that control the fate and functions of RBPs under stress. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138446417","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}
The Ccr4-Not complex is a global regulator of mRNA metabolism in eukaryotic cells that is most well-known to repress gene expression. Delivery of the complex to mRNAs through a multitude of distinct mechanisms accelerates their decay, yet Ccr4-Not also plays an important role in co-translational processes, such as co-translational association of proteins and delivery of translating mRNAs to organelles. The recent structure of Not5 interacting with the translated ribosome has brought to light that embedded information within the codon sequence can be monitored by recruitment of the Ccr4-Not complex to elongating ribosomes. Thereby, the Ccr4-Not complex is empowered with regulatory decisions determining the fate of proteins being synthesized and their encoding mRNAs. This review will focus on the roles of the complex in translation and dynamics of co-translation events. This article is categorized under: Translation > Mechanisms Translation > Regulation.
{"title":"Roles of the CCR4-Not complex in translation and dynamics of co-translation events.","authors":"Martine A Collart, Léna Audebert, Martin Bushell","doi":"10.1002/wrna.1827","DOIUrl":"10.1002/wrna.1827","url":null,"abstract":"<p><p>The Ccr4-Not complex is a global regulator of mRNA metabolism in eukaryotic cells that is most well-known to repress gene expression. Delivery of the complex to mRNAs through a multitude of distinct mechanisms accelerates their decay, yet Ccr4-Not also plays an important role in co-translational processes, such as co-translational association of proteins and delivery of translating mRNAs to organelles. The recent structure of Not5 interacting with the translated ribosome has brought to light that embedded information within the codon sequence can be monitored by recruitment of the Ccr4-Not complex to elongating ribosomes. Thereby, the Ccr4-Not complex is empowered with regulatory decisions determining the fate of proteins being synthesized and their encoding mRNAs. This review will focus on the roles of the complex in translation and dynamics of co-translation events. This article is categorized under: Translation > Mechanisms Translation > Regulation.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10909573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138446418","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}