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Wiley Interdisciplinary Reviews. RNA Mar 2021The 5' cap and 3' poly(A) tail of mRNA are known to synergistically regulate mRNA translation and stability. Recent computational and experimental studies revealed that... (Review)
Review
The 5' cap and 3' poly(A) tail of mRNA are known to synergistically regulate mRNA translation and stability. Recent computational and experimental studies revealed that both protein-coding and non-coding RNAs will fold with extensive intramolecular secondary structure, which will result in close distances between the sequence ends. This proximity of the ends is a sequence-independent, universal property of most RNAs. Only low-complexity sequences without guanosines are without secondary structure and exhibit end-to-end distances expected for RNA random coils. The innate proximity of RNA ends might have important biological implications that remain unexplored. In particular, the inherent compactness of mRNA might regulate translation initiation by facilitating the formation of protein complexes that bridge mRNA 5' and 3' ends. Additionally, the proximity of mRNA ends might mediate coupling of 3' deadenylation to 5' end mRNA decay. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems Translation > Translation Regulation.
Topics: Protein Biosynthesis; RNA; RNA Stability; RNA, Messenger
PubMed: 32597020
DOI: 10.1002/wrna.1611 -
Molecules and Cells Jan 2017Serine and arginine-rich (SR) proteins are RNA-binding proteins (RBPs) known as constitutive and alternative splicing regulators. As splicing is linked to... (Review)
Review
Serine and arginine-rich (SR) proteins are RNA-binding proteins (RBPs) known as constitutive and alternative splicing regulators. As splicing is linked to transcriptional and post-transcriptional steps, SR proteins are implicated in the regulation of multiple aspects of the gene expression program. Recent global analyses of SR-RNA interaction maps have advanced our understanding of SR-regulated gene expression. Diverse SR proteins play partially overlapping but distinct roles in transcription-coupled splicing and mRNA processing in the nucleus. In addition, shuttling SR proteins act as adaptors for mRNA export and as regulators for translation in the cytoplasm. This mini-review will summarize the roles of SR proteins as RNA binders, regulators, and connectors from transcription in the nucleus to translation in the cytoplasm.
Topics: Arginine; Humans; Protein Binding; Protein Biosynthesis; RNA; RNA Splicing; Serine; Serine-Arginine Splicing Factors
PubMed: 28152302
DOI: 10.14348/molcells.2017.2319 -
Cold Spring Harbor Perspectives in... Sep 2019Protein synthesis involves a complex machinery comprising numerous proteins and RNAs joined by noncovalent interactions. Its function is to link long chains of amino... (Review)
Review
Protein synthesis involves a complex machinery comprising numerous proteins and RNAs joined by noncovalent interactions. Its function is to link long chains of amino acids into proteins with precise sequences as encoded by the genome. Regulation of protein synthesis, called translational control, occurs both at a global level and at specific messenger RNAs (mRNAs). To understand how translation is regulated, knowledge of the molecular structures and kinetic interactions of its components is needed. This review focuses on the targets of translational control and the mechanisms employed.
Topics: 5' Untranslated Regions; Codon; Cytoplasm; Gene Expression Regulation; Genome; Kinetics; Phosphorylation; Protein Biosynthesis; Protein Conformation; Protein Processing, Post-Translational; Proteins; RNA; RNA, Messenger; Ribosomes
PubMed: 29959195
DOI: 10.1101/cshperspect.a032607 -
Trends in Biochemical Sciences Sep 2021Ribosomes that stall inappropriately during protein synthesis harbor proteotoxic components linked to cellular stress and neurodegenerative diseases. Molecular... (Review)
Review
Ribosomes that stall inappropriately during protein synthesis harbor proteotoxic components linked to cellular stress and neurodegenerative diseases. Molecular mechanisms that rescue stalled ribosomes must selectively detect rare aberrant translational complexes and process the heterogeneous components. Ribosome-associated quality control pathways eliminate problematic messenger RNAs and nascent proteins on stalled translational complexes. In addition, recent studies have uncovered general principles of stall recognition upstream of quality control pathways and fail-safe mechanisms that ensure nascent proteome integrity. Here, we discuss developments in our mechanistic understanding of the detection and rescue of stalled ribosomal complexes in eukaryotes.
Topics: Protein Biosynthesis; Protein Processing, Post-Translational; Proteins; RNA, Messenger; Ribosomes
PubMed: 33966939
DOI: 10.1016/j.tibs.2021.03.008 -
Biochemistry. Biokhimiia Aug 2013Translation, that is biosynthesis of polypeptides in accordance with information encoded in the genome, is one of the most important processes in the living cell, and it... (Review)
Review
Translation, that is biosynthesis of polypeptides in accordance with information encoded in the genome, is one of the most important processes in the living cell, and it has been in the spotlight of international research for many years. The mechanisms of protein biosynthesis in bacteria and in the eukaryotic cytoplasm are now understood in great detail. However, significantly less is known about translation in eukaryotic mitochondria, which is characterized by a number of unusual features. In this review, we summarize current knowledge about mitochondrial translation in different organisms while paying special attention to the aspects of this process that differ from cytoplasmic protein biosynthesis.
Topics: Animals; Humans; Mitochondria; Mitochondrial Proteins; Peptide Chain Elongation, Translational; Peptide Chain Initiation, Translational; Peptide Chain Termination, Translational; RNA
PubMed: 24228873
DOI: 10.1134/S0006297913080014 -
Accounts of Chemical Research May 2021RNA lies upstream of nearly all biology and functions as the central conduit of information exchange in all cells. RNA molecules encode information both in their primary... (Review)
Review
RNA lies upstream of nearly all biology and functions as the central conduit of information exchange in all cells. RNA molecules encode information both in their primary sequences and in complex structures that form when an RNA folds back on itself. From the time of discovery of mRNA in the late 1950s until quite recently, we had only a rudimentary understanding of RNA structure across vast regions of most messenger and noncoding RNAs. This deficit is now rapidly being addressed, especially by selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistry, mutational profiling (MaP), and closely related platform technologies that, collectively, create chemical microscopes for RNA. These technologies make it possible to interrogate RNA structure, quantitatively, at nucleotide resolution, and at large scales, for entire mRNAs, noncoding RNAs, and viral RNA genomes. By applying comprehensive structure probing to diverse problems, we and others are showing that control of biological function mediated by RNA structure is ubiquitous across prokaryotic and eukaryotic organisms.Work over the past decade using SHAPE-based analyses has clarified key principles. First, the method of RNA structure probing matters. SHAPE-MaP, with its direct and one-step readout that probes nearly every nucleotide by reaction at the 2'-hydroxyl, gives a more detailed and accurate readout than alternatives. Second, comprehensive chemical probing is essential. Focusing on fragments of large RNAs or using meta-gene or statistical analyses to compensate for sparse data sets misses critical features and often yields structure models with poor predictive power. Finally, every RNA has its own internal . There are myriad ways in which RNA structure modulates sequence accessibility, protein binding, translation, splice-site choice, phase separation, and other fundamental biological processes. In essentially every instance where we have applied rigorous and quantitative SHAPE technologies to study RNA structure-function interrelationships, new insights regarding biological regulatory mechanisms have emerged. RNA elements with more complex higher-order structures appear more likely to contain high-information-content clefts and pockets that bind small molecules, broadly informing a vigorous field of RNA-targeted drug discovery.The broad implications of this collective work are twofold. First, it is long past time to abandon depiction of large RNAs as simple noodle-like or gently flowing molecules. Instead, we need to emphasize that nearly all RNAs are punctuated with distinctive internal structures, a subset of which modulate function in profound ways. Second, structure probing should be an integral component of any effort that seeks to understand the functional nexuses and biological roles of large RNAs.
Topics: Acylation; RNA
PubMed: 33960770
DOI: 10.1021/acs.accounts.1c00118 -
Trends in Biochemical Sciences Apr 2021RNA G-quadruplexes (RG4s) are four-stranded structures known to control gene expression mechanisms, from transcription to protein synthesis, and DNA-related processes.... (Review)
Review
RNA G-quadruplexes (RG4s) are four-stranded structures known to control gene expression mechanisms, from transcription to protein synthesis, and DNA-related processes. Their potential impact on RNA biology allows these structures to shape cellular processes relevant to disease development, making their targeting for therapeutic purposes an attractive option. We review here the current knowledge on RG4s, focusing on the latest breakthroughs supporting the notion of transient structures that fluctuate dynamically in cellulo, their interplay with RNA modifications, their role in cell compartmentalization, and their deregulation impacting the host immune response. We emphasize RG4-binding proteins as determinants of their transient conformation and effectors of their biological functions.
Topics: Biology; DNA; G-Quadruplexes; Protein Biosynthesis; RNA
PubMed: 33303320
DOI: 10.1016/j.tibs.2020.11.001 -
Molecular Cell Oct 2014Cellular RNAs can be chemically modified over a hundred different ways. These modifications were once thought to be static, discrete, and utilized to fine-tune RNA... (Review)
Review
Cellular RNAs can be chemically modified over a hundred different ways. These modifications were once thought to be static, discrete, and utilized to fine-tune RNA structure and function. However, recent studies have revealed that some modifications, like mRNA methylation, can be reversed, and these reversible modifications may play active roles in regulating diverse biological processes. In this perspective, we summarize examples of dynamic RNA modifications that affect biological functions. We further propose that reversible modifications might occur on tRNA, rRNA, and other noncoding RNAs to regulate gene expression analogous to the reversible mRNA methylation.
Topics: Gene Expression Regulation; Methylation; Models, Genetic; RNA; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Ribosomal; RNA, Transfer
PubMed: 25280100
DOI: 10.1016/j.molcel.2014.09.001 -
Prion May 2016Amyloids are protein aggregates consisting of fibrils rich in β-sheets. Growth of amyloid fibrils occurs by the addition of protein molecules to the tip of an aggregate... (Review)
Review
Amyloids are protein aggregates consisting of fibrils rich in β-sheets. Growth of amyloid fibrils occurs by the addition of protein molecules to the tip of an aggregate with a concurrent change of a conformation. Thus, amyloids are self-propagating protein conformations. In certain cases these conformations are transmissible / infectious; they are known as prions. Initially, amyloids were discovered as pathological extracellular deposits occurring in different tissues and organs. To date, amyloids and prions have been associated with over 30 incurable diseases in humans and animals. However, a number of recent studies demonstrate that amyloids are also functionally involved in a variety of biological processes, from biofilm formation by bacteria, to long-term memory in animals. Interestingly, amyloid-forming proteins are highly overrepresented among cellular factors engaged in all stages of mRNA life cycle: from transcription and translation, to storage and degradation. Here we review rapidly accumulating data on functional and pathogenic amyloids associated with mRNA processing, and discuss possible significance of prion and amyloid networks in the modulation of key cellular functions.
Topics: Amyloid; Amyloidosis; Animals; Gene Expression Regulation; Humans; Prion Diseases; Prions; Protein Biosynthesis; Protein Conformation; Protein Interaction Maps; RNA; RNA Processing, Post-Transcriptional; RNA Stability; Transcription, Genetic
PubMed: 27248002
DOI: 10.1080/19336896.2016.1181253 -
Journal of Hematology & Oncology Jan 2017Circular RNAs (circRNAs) are a class of endogendous RNAs that form a covalently closed continuous loop and exist extensively in mammalian cells. Majority of circRNAs are... (Review)
Review
Circular RNAs (circRNAs) are a class of endogendous RNAs that form a covalently closed continuous loop and exist extensively in mammalian cells. Majority of circRNAs are conserved across species and often show tissue/developmental stage-specific expression. CircRNAs were first thought to be the result of splicing error; however, subsequent research shows that circRNAs can function as microRNA (miRNA) sponges and regulate splicing and transcription. Emerging evidence shows that circRNAs possess closely associated with human diseases, especially cancers, and may serve as better biomarkers. After miRNA and long noncoding RNA (lncRNA), circRNAs are becoming a new hotspot in the field of RNA of cancer. Here, we review biogenesis and metabolism of circRNAs, their functions, and potential roles in cancer.
Topics: Humans; Neoplasms; RNA; RNA Splicing; RNA, Circular; Transcription, Genetic
PubMed: 28049499
DOI: 10.1186/s13045-016-0370-2