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Molecular Cell Jul 2022Stress-induced condensation of mRNA and protein into massive cytosolic clusters is conserved across eukaryotes. Known as stress granules when visible by imaging, these... (Review)
Review
Stress-induced condensation of mRNA and protein into massive cytosolic clusters is conserved across eukaryotes. Known as stress granules when visible by imaging, these structures remarkably have no broadly accepted biological function, mechanism of formation or dispersal, or even molecular composition. As part of a larger surge of interest in biomolecular condensation, studies of stress granules and related RNA/protein condensates have increasingly probed the biochemical underpinnings of condensation. Here, we review open questions and recent advances, including the stages from initial condensate formation to accumulation in mature stress granules, mechanisms by which stress-induced condensates form and dissolve, and surprising twists in understanding the RNA components of stress granules and their role in condensation. We outline grand challenges in understanding stress-induced RNA condensation, centering on the unique and substantial barriers in the molecular study of cellular structures, such as stress granules, for which no biological function has been firmly established.
Topics: RNA; RNA, Messenger; Stress Granules
PubMed: 35662398
DOI: 10.1016/j.molcel.2022.05.014 -
Nature Cell Biology Apr 2022
Topics: RNA Processing, Post-Transcriptional; RNA, Messenger
PubMed: 35414018
DOI: 10.1038/s41556-022-00907-x -
Current Opinion in Chemical Biology Feb 2016Chemical modifications in cellular RNA are diverse and abundant. Commonly found in ribosomal RNA (rRNA), transfer RNA (tRNA), long-noncoding RNA (lncRNA), and small... (Review)
Review
Chemical modifications in cellular RNA are diverse and abundant. Commonly found in ribosomal RNA (rRNA), transfer RNA (tRNA), long-noncoding RNA (lncRNA), and small nuclear (snRNA), these components play various structural and functional roles. Until recently, the roles of chemical modifications within messenger RNA (mRNA) have been understudied. Recent maps of several mRNA modifications have suggested regulatory functions for these marks. This review summarizes recent advances in identifying and understanding biological roles of posttranscriptional mRNA modification, or 'RNA epigenetics', with an emphasis on the most common internal modification of eukaryotic mRNA, N(6)-methyladenosine (m(6)A). We also discuss YTH proteins as direct mediators of m(6)A function and the emerging role of this mark in a new layer of gene expression regulation.
Topics: Animals; Epigenesis, Genetic; Humans; RNA Processing, Post-Transcriptional; RNA, Messenger
PubMed: 26625014
DOI: 10.1016/j.cbpa.2015.10.024 -
Wiley Interdisciplinary Reviews. RNA Sep 2019The cellular stress response is a universal mechanism necessary for the survival of all organisms. This multifaceted process is primarily driven by regulation of gene... (Review)
Review
The cellular stress response is a universal mechanism necessary for the survival of all organisms. This multifaceted process is primarily driven by regulation of gene expression to produce an intracellular environment suitable for promoting cell survival and recovery. Posttranscriptional regulatory events are considered as critical mechanisms that modulate core characteristics of mRNA transcripts to promote cell adaptation to various assaults. While the impact of processes such as mRNA splicing, turnover, localization, and translation on the cellular stress response has been extensively studied, recent observations highlight the role of alternative polyadenylation (APA) in response to challenges such as oxidative stress, heat shock, and starvation. The role of APA is comprehensive with far reaching effects on mRNA stability, mRNA localization, and protein coding sequences. Nonetheless, APA remains a relatively unappreciated mode of gene regulation despite its role in regulating key mediators of the stress response. The goal of this review is to provide an overview of the recent advances in our understanding of the various ways by which APA affects cell adaptation to its environment and discuss how a defect in APA could have deleterious consequences on cell survival. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Processing > 3' End Processing.
Topics: Humans; Oxidative Stress; Polyadenylation; RNA, Messenger; Stress, Physiological
PubMed: 31050180
DOI: 10.1002/wrna.1540 -
Journal of Molecular Endocrinology Aug 2016Our understanding of the extent of microRNA-based gene regulation has expanded in an impressive pace over the past decade. Now, we are beginning to better appreciate the... (Review)
Review
Our understanding of the extent of microRNA-based gene regulation has expanded in an impressive pace over the past decade. Now, we are beginning to better appreciate the role of 3'-UTR (untranslated region) cis-elements which harbor not only microRNA but also RNA-binding protein (RBP) binding sites that have significant effect on the stability and translational rate of mRNAs. To add further complexity, alternative polyadenylation (APA) emerges as a widespread mechanism to regulate gene expression by producing shorter or longer mRNA isoforms that differ in the length of their 3'-UTRs or even coding sequences. Resulting shorter mRNA isoforms generally lack cis-elements where trans-acting factors bind, and hence are differentially regulated compared with the longer isoforms. This review focuses on the RBPs involved in APA regulation and their action mechanisms on APA-generated isoforms. A better understanding of the complex interactions between APA and RBPs is promising for mechanistic and clinical implications including biomarker discovery and new therapeutic approaches.
Topics: 3' Untranslated Regions; Animals; Gene Expression Regulation; Humans; Polyadenylation; Protein Binding; RNA Isoforms; RNA, Messenger; RNA-Binding Proteins
PubMed: 27208003
DOI: 10.1530/JME-16-0070 -
Angewandte Chemie (International Ed. in... Jun 2023A major stage in the expression of genes is the translation of messenger RNA (mRNA), and the regulation of this process is essential for protein production in cells. How... (Review)
Review
A major stage in the expression of genes is the translation of messenger RNA (mRNA), and the regulation of this process is essential for protein production in cells. How tightly controlled gene expression can be spatially and temporally, is particularly evident in polar cells and embryonic development. We need tools to dissect these complex processes, if we wish to understand the underlying links, especially the difficulties brought on by malfunction. External bioorthogonal triggers are very helpful in this area, if they let us precisely control where and when a process is started. Equipping nucleic acids with light-responsive groups has proven to be an effective approach to examine the dynamic regulatory route of mRNA translation in living cells. In this review, we present an overview of the most recent methods for optochemically controlling translation, focusing on cis-acting technologies.
Topics: RNA, Messenger; Eukaryota; Gene Expression Regulation; Proteins; Protein Biosynthesis
PubMed: 36929624
DOI: 10.1002/anie.202301778 -
Nature Chemical Biology Mar 2023
Topics: Methylation; RNA, Messenger
PubMed: 36854743
DOI: 10.1038/s41589-023-01290-w -
Nature Medicine Sep 2018
Topics: Animals; Clinical Trials as Topic; Genetic Engineering; Mice; Proteins; RNA, Messenger
PubMed: 30139958
DOI: 10.1038/s41591-018-0183-7 -
Annual Review of Plant Biology Apr 2016RNA transcripts fold into secondary structures via intricate patterns of base pairing. These secondary structures impart catalytic, ligand binding, and scaffolding... (Review)
Review
RNA transcripts fold into secondary structures via intricate patterns of base pairing. These secondary structures impart catalytic, ligand binding, and scaffolding functions to a wide array of RNAs, forming a critical node of biological regulation. Among their many functions, RNA structural elements modulate epigenetic marks, alter mRNA stability and translation, regulate alternative splicing, transduce signals, and scaffold large macromolecular complexes. Thus, the study of RNA secondary structure is critical to understanding the function and regulation of RNA transcripts. Here, we review the origins, form, and function of RNA secondary structure, focusing on plants. We then provide an overview of methods for probing secondary structure, from physical methods such as X-ray crystallography and nuclear magnetic resonance (NMR) imaging to chemical and nuclease probing methods. Combining these latter methods with high-throughput sequencing has enabled them to scale across whole transcriptomes, yielding tremendous new insights into the form and function of RNA secondary structure.
Topics: Gene Expression Regulation, Plant; Nucleic Acid Conformation; Plants; RNA, Messenger; RNA, Plant; Transcriptome
PubMed: 26865341
DOI: 10.1146/annurev-arplant-043015-111754 -
Annual Review of Virology Sep 2023Protein synthesis by the ribosome is the final stage of biological information transfer and represents an irreversible commitment to gene expression. Accurate... (Review)
Review
Protein synthesis by the ribosome is the final stage of biological information transfer and represents an irreversible commitment to gene expression. Accurate translation of messenger RNA is therefore essential to all life, and spontaneous errors by the translational machinery are highly infrequent (∼1/100,000 codons). Programmed -1 ribosomal frameshifting (-1PRF) is a mechanism in which the elongating ribosome is induced at high frequency to slip backward by one nucleotide at a defined position and to continue translation in the new reading frame. This is exploited as a translational regulation strategy by hundreds of RNA viruses, which rely on -1PRF during genome translation to control the stoichiometry of viral proteins. While early investigations of -1PRF focused on virological and biochemical aspects, the application of X-ray crystallography and cryo-electron microscopy (cryo-EM), and the advent of deep sequencing and single-molecule approaches have revealed unexpected structural diversity and mechanistic complexity. Molecular players from several model systems have now been characterized in detail, both in isolation and, more recently, in the context of the elongating ribosome. Here we provide a summary of recent advances and discuss to what extent a general model for -1PRF remains a useful way of thinking.
Topics: Frameshifting, Ribosomal; Cryoelectron Microscopy; Ribosomes; RNA, Messenger; RNA Viruses; RNA, Viral
PubMed: 37339768
DOI: 10.1146/annurev-virology-111821-120646