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Philosophical Transactions of the Royal... Nov 2018RNA degradation is a key process in the regulation of gene expression. In all organisms, RNA degradation participates in controlling coding and non-coding RNA levels in...
RNA degradation is a key process in the regulation of gene expression. In all organisms, RNA degradation participates in controlling coding and non-coding RNA levels in response to developmental and environmental cues. RNA degradation is also crucial for the elimination of defective RNAs. Those defective RNAs are mostly produced by 'mistakes' made by the RNA processing machinery during the maturation of functional transcripts from their precursors. The constant control of RNA quality prevents potential deleterious effects caused by the accumulation of aberrant non-coding transcripts or by the translation of defective messenger RNAs (mRNAs). Prokaryotic and eukaryotic organisms are also under the constant threat of attacks from pathogens, mostly viruses, and one common line of defence involves the ribonucleolytic digestion of the invader's RNA. Finally, mutations in components involved in RNA degradation are associated with numerous diseases in humans, and this together with the multiplicity of its roles illustrates the biological importance of RNA degradation. RNA degradation is mostly viewed as a default pathway: any functional RNA (including a successful pathogenic RNA) must be protected from the scavenging RNA degradation machinery. Yet, this protection must be temporary, and it will be overcome at one point because the ultimate fate of any cellular RNA is to be eliminated. This special issue focuses on modifications deposited at the 5' or the 3' extremities of RNA, and how these modifications control RNA stability or degradation.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.
Topics: Eukaryota; Humans; Prokaryotic Cells; RNA Stability; RNA, Messenger; RNA, Untranslated
PubMed: 30397097
DOI: 10.1098/rstb.2018.0160 -
Philosophical Transactions of the Royal... Nov 2018RNA uridylation consists of the untemplated addition of uridines at the 3' extremity of an RNA molecule. RNA uridylation is catalysed by terminal uridylyltransferases... (Review)
Review
RNA uridylation consists of the untemplated addition of uridines at the 3' extremity of an RNA molecule. RNA uridylation is catalysed by terminal uridylyltransferases (TUTases), which form a subgroup of the terminal nucleotidyltransferase family, to which poly(A) polymerases also belong. The key role of RNA uridylation is to regulate RNA degradation in a variety of eukaryotes, including fission yeast, plants and animals. In plants, RNA uridylation has been mostly studied in two model species, the green algae and the flowering plant Plant TUTases target a variety of RNA substrates, differing in size and function. These RNA substrates include microRNAs (miRNAs), small interfering silencing RNAs (siRNAs), ribosomal RNAs (rRNAs), messenger RNAs (mRNAs) and mRNA fragments generated during post-transcriptional gene silencing. Viral RNAs can also get uridylated during plant infection. We describe here the evolutionary history of plant TUTases and we summarize the diverse molecular functions of uridylation during RNA degradation processes in plants. We also outline key points of future research.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.
Topics: Arabidopsis; Chlamydomonas reinhardtii; Plants; RNA; RNA Interference; RNA Stability; Uridine
PubMed: 30397100
DOI: 10.1098/rstb.2018.0163 -
Developmental Cell Dec 2022Embryonic stem cells (ESCs) are self-renewing and pluripotent. In recent years, factors that control pluripotency, mostly nuclear, have been identified. To identify...
Embryonic stem cells (ESCs) are self-renewing and pluripotent. In recent years, factors that control pluripotency, mostly nuclear, have been identified. To identify non-nuclear regulators of ESCs, we screened an endogenously labeled fluorescent fusion-protein library in mouse ESCs. One of the more compelling hits was the cell-cycle-associated protein 1 (CAPRIN1). CAPRIN1 knockout had little effect in ESCs, but it significantly altered differentiation and gene expression programs. Using RIP-seq and SLAM-seq, we found that CAPRIN1 associates with, and promotes the degradation of, thousands of RNA transcripts. CAPRIN1 interactome identified XRN2 as the likely ribonuclease. Upon early ESC differentiation, XRN2 is located in the nucleus and colocalizes with CAPRIN1 in small RNA granules in a CAPRIN1-dependent manner. We propose that CAPRIN1 regulates an RNA degradation pathway operating during early ESC differentiation, thus eliminating undesired spuriously transcribed transcripts in ESCs.
Topics: Animals; Mice; Cell Cycle; Cell Cycle Proteins; Cell Differentiation; Mouse Embryonic Stem Cells; RNA Stability; Exoribonucleases
PubMed: 36495875
DOI: 10.1016/j.devcel.2022.11.014 -
Molecular Cell Apr 2021Eukaryotic cells integrate multiple quality control (QC) responses during protein synthesis in the cytoplasm. These QC responses are signaled by slow or stalled... (Review)
Review
Eukaryotic cells integrate multiple quality control (QC) responses during protein synthesis in the cytoplasm. These QC responses are signaled by slow or stalled elongating ribosomes. Depending on the nature of the delay, the signal may lead to translational repression, messenger RNA decay, ribosome rescue, and/or nascent protein degradation. Here, we discuss how the structure and composition of an elongating ribosome in a troubled state determine the downstream quality control pathway(s) that ensue. We highlight the intersecting pathways involved in RNA decay and the crosstalk that occurs between RNA decay and ribosome rescue.
Topics: Animals; Eukaryotic Cells; Humans; Protein Biosynthesis; RNA Stability; RNA, Messenger; Ribosomes
PubMed: 33713598
DOI: 10.1016/j.molcel.2021.02.022 -
Molecular Microbiology Aug 2021Although riboswitches have long been known to regulate translation initiation and transcription termination, a growing body of evidence indicates that they can also... (Review)
Review
Although riboswitches have long been known to regulate translation initiation and transcription termination, a growing body of evidence indicates that they can also control bacterial RNA lifetimes by acting directly to hasten or impede RNA degradation. Ligand binding to the aptamer domain of a riboswitch can accelerate RNA decay by triggering a conformational change that exposes sites to endonucleolytic cleavage or by catalyzing the self-cleavage of a prefolded ribozyme. Alternatively, the conformational change induced by ligand binding can protect RNA from degradation by blocking access to an RNA terminus or internal region that would otherwise be susceptible to attack by an exonuclease or endonuclease. Such changes in RNA longevity often accompany a parallel effect of the same riboswitch on translation or transcription. Consequently, a single riboswitch aptamer may govern the function of multiple effector elements (expression platforms) that are co-resident within a transcript and act independently of one another.
Topics: Bacteria; Endonucleases; Gene Expression Regulation, Bacterial; Nucleic Acid Conformation; RNA Stability; RNA, Bacterial; Riboswitch
PubMed: 33797153
DOI: 10.1111/mmi.14723 -
Wiley Interdisciplinary Reviews. RNA 2011Although the first poly(A) polymerase (PAP) was discovered in Escherichia coli in 1962, the study of polyadenylation in bacteria was largely ignored for the next 30... (Review)
Review
Although the first poly(A) polymerase (PAP) was discovered in Escherichia coli in 1962, the study of polyadenylation in bacteria was largely ignored for the next 30 years. However, with the identification of the structural gene for E. coli PAP I in 1992, it became possible to analyze polyadenylation using both biochemical and genetic approaches. Subsequently, it has been shown that polyadenylation plays a multifunctional role in prokaryotic RNA metabolism. Although the bulk of our current understanding of prokaryotic polyadenylation comes from studies on E. coli, recent limited experiments with Cyanobacteria, organelles, and Archaea have widened our view on the diversity, complexity, and universality of the polyadenylation process. For example, the identification of polynucleotide phosphorylase (PNPase), a reversible phosphorolytic enzyme that is highly conserved in bacteria, as an additional PAP in E. coli caught everyone by surprise. In fact, PNPase has now been shown to be the source of post-transcriptional RNA modifications in a wide range of cells of prokaryotic origin including those that lack a eubacterial PAP homolog. Accordingly, the past few years have witnessed increased interest in the mechanism and role of post-transcriptional modifications in all species of prokaryotic origin. However, the fact that many of the poly(A) tails are very short and unstable as well as the presence of polynucleotide tails has posed significant technical challenges to the scientific community trying to unravel the mystery of polyadenylation in prokaryotes. This review discusses the current state of knowledge regarding polyadenylation and its functions in bacteria, organelles, and Archaea.
Topics: Animals; Archaea; Bacteria; Base Sequence; Humans; Models, Biological; Molecular Sequence Data; Organelles; Polyadenylation; Quality Control; RNA Stability
PubMed: 21344039
DOI: 10.1002/wrna.51 -
Transcription Nov 2023Eukaryotic cells rely upon dynamic, multifaceted regulation at each step of RNA biogenesis to maintain mRNA pools and ensure normal protein synthesis. Studies in budding... (Review)
Review
Eukaryotic cells rely upon dynamic, multifaceted regulation at each step of RNA biogenesis to maintain mRNA pools and ensure normal protein synthesis. Studies in budding yeast indicate a buffering phenomenon that preserves global mRNA levels through the reciprocal balancing of RNA synthesis rates and mRNA decay. In short, changes in transcription impact the efficiency of mRNA degradation and defects in either nuclear or cytoplasmic mRNA degradation are somehow sensed and relayed to control a compensatory change in mRNA transcription rates. Here, we review current views on molecular mechanisms that might explain this apparent bidirectional sensing process that ensures homeostasis of the stable mRNA pool.
Topics: RNA, Messenger; Transcription, Genetic; Cytoplasm; Homeostasis; RNA Stability
PubMed: 36843061
DOI: 10.1080/21541264.2023.2183684 -
Plant Science : An International... May 2022RNA degradation is an important process for controlling gene expression and is mediated by decapping / deadenylation-dependent or endonucleolytic cleavage-dependent RNA... (Review)
Review
RNA degradation is an important process for controlling gene expression and is mediated by decapping / deadenylation-dependent or endonucleolytic cleavage-dependent RNA degradation mechanisms. High-throughput sequencing of RNA degradation intermediates was initially developed in Arabidopsis thaliana and similar RNA degradome sequencing methods were conducted in other eukaryotes. However, interpreting results obtained by these sequencing methods is fragmented, and an overview is needed. Here we review the findings and limitations of these sequencing methods and discuss the missing experiments needed to understand RNA degradation intermediates accurately. This review provides direction for future research on RNA degradation and is a reference for RNA degradome studies in other species.
Topics: Arabidopsis; Base Sequence; Plants; RNA Stability; Sequence Analysis, RNA
PubMed: 35351296
DOI: 10.1016/j.plantsci.2022.111241 -
Molecular Cell Jan 2023N6-methyladenosine (m6A), a widespread destabilizing mark on mRNA, is non-uniformly distributed across the transcriptome, yet the basis for its selective deposition is...
N6-methyladenosine (m6A), a widespread destabilizing mark on mRNA, is non-uniformly distributed across the transcriptome, yet the basis for its selective deposition is unknown. Here, we propose that m6A deposition is not selective. Instead, it is exclusion based: m6A consensus motifs are methylated by default, unless they are within a window of ∼100 nt from a splice junction. A simple model which we extensively validate, relying exclusively on presence of m6A motifs and exon-intron architecture, allows in silico recapitulation of experimentally measured m6A profiles. We provide evidence that exclusion from splice junctions is mediated by the exon junction complex (EJC), potentially via physical occlusion, and that previously observed associations between exon-intron architecture and mRNA decay are mechanistically mediated via m6A. Our findings establish a mechanism coupling nuclear mRNA splicing and packaging with the covalent installation of m6A, in turn controlling cytoplasmic decay.
Topics: RNA, Messenger; RNA Splicing; Transcriptome; RNA Stability; Exons
PubMed: 36599352
DOI: 10.1016/j.molcel.2022.12.026 -
BMB Reports Jun 2023RNAs are pivotal molecules acting as messengers of genetic information and regulatory molecules for cellular development and survival. From birth to death, RNAs face... (Review)
Review
RNAs are pivotal molecules acting as messengers of genetic information and regulatory molecules for cellular development and survival. From birth to death, RNAs face constant cellular decision for the precise control of cellular function and activity. Most eukaryotic cells employ conserved machineries for RNA decay including RNA silencing and RNA quality control (RQC). In plants, RQC monitors endogenous RNAs and degrades aberrant and dysfunctional species, whereas RNA silencing promotes RNA degradation to repress the expression of selected endogenous RNAs or exogenous RNA derived from transgenes and virus. Interestingly, emerging evidences have indicated that RQC and RNA silencing interact with each by sharing target RNAs and regulatory components. Such interaction should be tightly organized for proper cellular survival. However, it is still elusive that how each machinery specifically recognizes target RNAs. In this review, we summarize recent advances on RNA silencing and RQC pathway and discuss potential mechanisms underlying the interaction between the two machineries. [BMB Reports 2023; 56(6): 321-325].
Topics: RNA Interference; RNA, Small Interfering; Plants; RNA Stability; Quality Control
PubMed: 37156633
DOI: 10.5483/BMBRep.2023-0049