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Journal of Molecular Biology Jul 2017G-quadruplexes (G4s) are extremely stable DNA or RNA secondary structures formed by sequences rich in guanine. These structures are implicated in many essential cellular... (Review)
Review
G-quadruplexes (G4s) are extremely stable DNA or RNA secondary structures formed by sequences rich in guanine. These structures are implicated in many essential cellular processes, and the number of biological functions attributed to them continues to grow. While DNA G4s are well understood on structural and, to some extent, functional levels, RNA G4s and their functions have received less attention. The presence of bona fide RNA G4s in cells has long been a matter of debate. The development of G4-specific antibodies and ligands hinted on their presence in vivo, but recent advances in RNA sequencing coupled with chemical footprinting suggested the opposite. In this review, we will critically discuss the biology of RNA G4s focusing on the molecular mechanisms underlying their proposed functions.
Topics: G-Quadruplexes; Gene Expression Regulation; Protein Biosynthesis; RNA, Messenger; Transcription, Genetic
PubMed: 28554731
DOI: 10.1016/j.jmb.2017.05.017 -
International Journal of Molecular... Mar 2021Most protein-coding genes in eukaryotes possess at least two poly(A) sites, and alternative polyadenylation is considered a contributing factor to transcriptomic and... (Review)
Review
Most protein-coding genes in eukaryotes possess at least two poly(A) sites, and alternative polyadenylation is considered a contributing factor to transcriptomic and proteomic diversity. Following transcription, a nascent RNA usually undergoes capping, splicing, cleavage, and polyadenylation, resulting in a mature messenger RNA (mRNA); however, increasing evidence suggests that transcription and RNA processing are coupled. Plants, which must produce rapid responses to environmental changes because of their limited mobility, exhibit such coupling. In this review, we summarize recent advances in our understanding of the coupling of transcription with RNA processing in plants, and we describe the possible spatial environment and important proteins involved. Moreover, we describe how liquid-liquid phase separation, mediated by the C-terminal domain of RNA polymerase II and RNA processing factors with intrinsically disordered regions, enables efficient co-transcriptional mRNA processing in plants.
Topics: Gene Expression Regulation, Plant; Polyadenylation; RNA, Messenger; RNA, Plant; Transcription, Genetic
PubMed: 33804866
DOI: 10.3390/ijms22073300 -
Annals of the New York Academy of... Jul 2019In bacteria, trans-translation is the primary quality control mechanism for rescuing ribosomes arrested during translation. This key process is universally conserved and... (Review)
Review
In bacteria, trans-translation is the primary quality control mechanism for rescuing ribosomes arrested during translation. This key process is universally conserved and plays a crucial role in the viability and virulence of all bacteria. It is performed by transfer-messenger RNA (tmRNA) and its protein partner small protein B (SmpB). Here, we show that tmRNA is a key molecule that could have given birth to modern protein synthesis. The traces of an ancient RNA world persist in the structure of modern tmRNA, suggesting its old origins. Therefore, since it has both tRNA and mRNA functions, tmRNA could be the missing link that allowed modern genetic code to be read by the ribosome.
Topics: Animals; Humans; Protein Biosynthesis; Protein Structure, Secondary; RNA, Bacterial; RNA, Messenger; RNA, Transfer
PubMed: 30815901
DOI: 10.1111/nyas.14035 -
Nature Jan 2024
Topics: RNA, Messenger; RNA; Proteins
PubMed: 38093050
DOI: 10.1038/d41586-023-03787-9 -
Wiley Interdisciplinary Reviews. RNA Sep 2016RNAs, which play significant roles in many fundamental biological processes of life, fold into sophisticated and precise structures. RNA folding is a dynamic and... (Review)
Review
RNAs, which play significant roles in many fundamental biological processes of life, fold into sophisticated and precise structures. RNA folding is a dynamic and intricate process, which conformation transition of coding and noncoding RNAs form the primary elements of genetic regulation. The cellular environment contains various intrinsic and extrinsic factors that potentially affect RNA folding in vivo, and experimental and theoretical evidence increasingly indicates that the highly flexible features of the RNA structure are affected by these factors, which include the flanking sequence context, physiochemical conditions, cis RNA-RNA interactions, and RNA interactions with other molecules. Furthermore, distinct RNA structures have been identified that govern almost all steps of biological processes in cells, including transcriptional activation and termination, transcriptional mutagenesis, 5'-capping, splicing, 3'-polyadenylation, mRNA export and localization, and translation. Here, we briefly summarize the dynamic and complex features of RNA folding along with a wide variety of intrinsic and extrinsic factors that affect RNA folding. We then provide several examples to elaborate RNA structure-mediated regulation at the transcriptional and posttranscriptional levels. Finally, we illustrate the regulatory roles of RNA structure and discuss advances pertaining to RNA structure in plants. WIREs RNA 2016, 7:562-574. doi: 10.1002/wrna.1350 For further resources related to this article, please visit the WIREs website.
Topics: Eukaryota; Gene Expression Regulation; Nucleic Acid Conformation; Prokaryotic Cells; RNA Folding; RNA, Messenger; Transcription, Genetic
PubMed: 27028291
DOI: 10.1002/wrna.1350 -
Seminars in Cell & Developmental Biology Dec 2015
Topics: Animals; Gene Expression Regulation, Developmental; Humans; Morphogenesis; Protein Biosynthesis; RNA, Messenger; RNA, Untranslated; Transcription, Genetic
PubMed: 26686814
DOI: 10.1016/j.semcdb.2015.11.016 -
Cold Spring Harbor Perspectives in... May 2018RNA decay plays a major role in regulating gene expression and is tightly networked with other aspects of gene expression to effectively coordinate post-transcriptional... (Review)
Review
RNA decay plays a major role in regulating gene expression and is tightly networked with other aspects of gene expression to effectively coordinate post-transcriptional regulation. The goal of this work is to provide an overview of the major factors and pathways of general messenger RNA (mRNA) decay in eukaryotic cells, and then discuss the effective interplay of this cytoplasmic process with the protein synthesis machinery. Given the transcript-specific and fluid nature of mRNA stability in response to changing cellular conditions, understanding the fundamental networking between RNA decay and translation will provide a foundation for a complete mechanistic understanding of this important aspect of cell biology.
Topics: Eukaryota; Gene Expression Regulation; Models, Genetic; Protein Biosynthesis; RNA Stability; RNA, Messenger
PubMed: 29311343
DOI: 10.1101/cshperspect.a032839 -
The New England Journal of Medicine Jun 2023
Topics: Humans; RNA, Messenger; Neurodegenerative Diseases; Protein Biosynthesis; Gene Expression Regulation
PubMed: 37256994
DOI: 10.1056/NEJMc2304387 -
Wiley Interdisciplinary Reviews. RNA Jul 2020Cells use chemical modifications to alter the sterics, charge, and conformations of large biomolecules, modulating their biogenesis, function, and stability. Until... (Review)
Review
Cells use chemical modifications to alter the sterics, charge, and conformations of large biomolecules, modulating their biogenesis, function, and stability. Until recently post-transcriptional RNA modifications were thought to be largely limited to nonprotein coding RNA species. However, this dogma has rapidly transformed with the discovery of a host of modifications in protein coding messenger RNAs (mRNAs). Recent advancements in genome-wide sequencing technologies have enabled the identification of mRNA modifications as a potential new frontier in gene regulation-leading to the development of the epitranscriptome field. As a result, there has been a flurry of multiple groundbreaking discoveries, including new modifications, nucleoside modifying enzymes ("writers" and "erasers"), and RNA binding proteins that recognize chemical modifications ("readers"). These discoveries opened the door to understanding how post-transcriptional mRNA modifications can modulate the mRNA lifecycle, and established a link between the epitranscriptome and human health and disease. Despite a rapidly growing recognition of their importance, fundamental questions regarding the identity, prevalence, and functional consequences of mRNA modifications remain to be answered. Here, we highlight quantitative studies that characterize mRNA modification abundance, frequency, and interactions with cellular machinery. As the field progresses, we see a need for the further integration of quantitative and reductionist approaches to complement transcriptome wide studies in order to establish a molecular-level framework for understanding the consequences of mRNA chemical modifications on biological processes. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Processing > RNA Editing and Modification.
Topics: Humans; Nucleic Acid Conformation; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA-Binding Proteins
PubMed: 31960607
DOI: 10.1002/wrna.1586 -
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