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Genetics Jul 2012All RNA species in yeast cells are subject to turnover. Work over the past 20 years has defined degradation mechanisms for messenger RNAs, transfer RNAs, ribosomal RNAs,... (Review)
Review
All RNA species in yeast cells are subject to turnover. Work over the past 20 years has defined degradation mechanisms for messenger RNAs, transfer RNAs, ribosomal RNAs, and noncoding RNAs. In addition, numerous quality control mechanisms that target aberrant RNAs have been identified. Generally, each decay mechanism contains factors that funnel RNA substrates to abundant exo- and/or endonucleases. Key issues for future work include determining the mechanisms that control the specificity of RNA degradation and how RNA degradation processes interact with translation, RNA transport, and other cellular processes.
Topics: Animals; Cytoplasm; RNA Stability; RNA, Fungal; Saccharomyces cerevisiae
PubMed: 22785621
DOI: 10.1534/genetics.111.137265 -
Molecular Microbiology Jun 2012RNA processing and degradation are key processes in the control of transcript accumulation and thus in the control of gene expression. In Escherichia coli, the... (Review)
Review
RNA processing and degradation are key processes in the control of transcript accumulation and thus in the control of gene expression. In Escherichia coli, the underlying mechanisms and components of RNA decay are well characterized. By contrast, Gram-positive bacteria do not possess several important players of E. coli RNA degradation, most notably the essential enzyme RNase E. Recent research on the model Gram-positive organism, Bacillus subtilis, has identified the essential RNases J1 and Y as crucial enzymes in RNA degradation. While RNase J1 is the first bacterial exoribonuclease with 5'-to-3' processivity, RNase Y is the founding member of a novel class of endoribonucleases. Both RNase J1 and RNase Y have a broad impact on the stability of B. subtilis mRNAs; a depletion of either enzyme affects more than 25% of all mRNAs. RNases J1 and Y as well as RNase J2, the polynucleotide phosphorylase PNPase, the RNA helicase CshA and the glycolytic enzymes enolase and phosphofructokinase have been proposed to form a complex, the RNA degradosome of B. subtilis. This review presents a model, based on recent published data, of RNA degradation in B. subtilis. Degradation is initiated by RNase Y-dependent endonucleolytic cleavage, followed by processive exoribonucleolysis of the generated fragments both in 3'-to-5' and in 5'-to-3' directions. The implications of these findings for pathogenic Gram-positive bacteria are also discussed.
Topics: Bacillus subtilis; Endoribonucleases; Exoribonucleases; Models, Biological; Models, Molecular; RNA; RNA Stability
PubMed: 22568516
DOI: 10.1111/j.1365-2958.2012.08072.x -
International Journal of Molecular... Dec 2021The genome is pervasively transcribed across various species, yielding numerous non-coding RNAs. As a counterbalance for pervasive transcription, various organisms have... (Review)
Review
The genome is pervasively transcribed across various species, yielding numerous non-coding RNAs. As a counterbalance for pervasive transcription, various organisms have a nuclear RNA exosome complex, whose structure is well conserved between yeast and mammalian cells. The RNA exosome not only regulates the processing of stable RNA species, such as rRNAs, tRNAs, small nucleolar RNAs, and small nuclear RNAs, but also plays a central role in RNA surveillance by degrading many unstable RNAs and misprocessed pre-mRNAs. In addition, associated cofactors of RNA exosome direct the exosome to distinct classes of RNA substrates, suggesting divergent and/or multi-layer control of RNA quality in the cell. While the RNA exosome is essential for cell viability and influences various cellular processes, mutations and alterations in the RNA exosome components are linked to the collection of rare diseases and various diseases including cancer, respectively. The present review summarizes the relationships between pervasive transcription and RNA exosome, including evolutionary crosstalk, mechanisms of RNA exosome-mediated RNA surveillance, and physiopathological effects of perturbation of RNA exosome.
Topics: Animals; Exosome Multienzyme Ribonuclease Complex; Genome; Humans; RNA; RNA Stability; RNA, Nuclear; Transcription, Genetic
PubMed: 34948199
DOI: 10.3390/ijms222413401 -
Nucleic Acids Research 2006Degradation of RNA plays a central role in RNA metabolism. In recent years, our knowledge of the mechanisms of RNA degradation has increased considerably with discovery... (Comparative Study)
Comparative Study Review
Degradation of RNA plays a central role in RNA metabolism. In recent years, our knowledge of the mechanisms of RNA degradation has increased considerably with discovery of the participating RNases and analysis of mutants affected in the various degradative pathways. Among these processes, mRNA decay and stable RNA degradation generally have been considered distinct, and also separate from RNA maturation. In this review, each of these processes is described, as it is currently understood in bacteria. The picture that emerges is that decay of mRNA and degradation of stable RNA share many common features, and that their initial steps also overlap with those of RNA maturation. Thus, bacterial cells do not contain dedicated machinery for degradation of different classes of RNA or for different processes. Rather, only the specificity of the RNase and the accessibility of the substrate determine whether or not a particular RNA will be acted upon.
Topics: Bacteria; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Bacterial; RNA, Messenger; Ribonucleases
PubMed: 16452296
DOI: 10.1093/nar/gkj472 -
The Journal of Biological Chemistry Sep 2023The levels of non-coding RNAs (ncRNAs) are regulated by transcription, RNA processing, and RNA degradation pathways. One mechanism for the degradation of ncRNAs involves... (Review)
Review
The levels of non-coding RNAs (ncRNAs) are regulated by transcription, RNA processing, and RNA degradation pathways. One mechanism for the degradation of ncRNAs involves the addition of oligo(A) tails by non-canonical poly(A) polymerases, which then recruit processive sequence-independent 3' to 5' exonucleases for RNA degradation. This pathway of decay is also regulated by three 3' to 5' exoribonucleases, USB1, PARN, and TOE1, which remove oligo(A) tails and thereby can protect ncRNAs from decay in a manner analogous to the deubiquitination of proteins. Loss-of-function mutations in these genes lead to premature degradation of some ncRNAs and lead to specific human diseases such as Poikiloderma with Neutropenia (PN) for USB1, Dyskeratosis Congenita (DC) for PARN and Pontocerebellar Hypoplasia type 7 (PCH7) for TOE1. Herein, we review the biochemical properties of USB1, PARN, and TOE1, how they modulate ncRNA levels, and their roles in human diseases.
Topics: Humans; Dyskeratosis Congenita; Exoribonucleases; Neutropenia; RNA Stability; RNA, Untranslated; Loss of Function Mutation
PubMed: 37544646
DOI: 10.1016/j.jbc.2023.105139 -
Molecular Cell Jul 2022In mammalian cells, spurious transcription results in a vast repertoire of unproductive non-coding RNAs, whose deleterious accumulation is prevented by rapid decay. The...
In mammalian cells, spurious transcription results in a vast repertoire of unproductive non-coding RNAs, whose deleterious accumulation is prevented by rapid decay. The nuclear exosome targeting (NEXT) complex plays a central role in directing non-functional transcripts to exosome-mediated degradation, but the structural and molecular mechanisms remain enigmatic. Here, we elucidated the architecture of the human NEXT complex, showing that it exists as a dimer of MTR4-ZCCHC8-RBM7 heterotrimers. Dimerization preconfigures the major MTR4-binding region of ZCCHC8 and arranges the two MTR4 helicases opposite to each other, with each protomer able to function on many types of RNAs. In the inactive state of the complex, the 3' end of an RNA substrate is enclosed in the MTR4 helicase channel by a ZCCHC8 C-terminal gatekeeping domain. The architecture of a NEXT-exosome assembly points to the molecular and regulatory mechanisms with which the NEXT complex guides RNA substrates to the exosome.
Topics: Cell Nucleus; DEAD-box RNA Helicases; DNA Helicases; Exosome Multienzyme Ribonuclease Complex; Exosomes; Humans; Protein Binding; RNA; RNA Helicases; RNA Stability
PubMed: 35688157
DOI: 10.1016/j.molcel.2022.04.011 -
Annual Review of Genetics 2014mRNA degradation is an important mechanism for controlling gene expression in bacterial cells. This process involves the orderly action of a battery of cellular... (Review)
Review
mRNA degradation is an important mechanism for controlling gene expression in bacterial cells. This process involves the orderly action of a battery of cellular endonucleases and exonucleases, some universal and others present only in certain species. These ribonucleases function with the assistance of ancillary enzymes that covalently modify the 5' or 3' end of RNA or unwind base-paired regions. Triggered by initiating events at either the 5' terminus or an internal site, mRNA decay occurs at diverse rates that are transcript specific and governed by RNA sequence and structure, translating ribosomes, and bound sRNAs or proteins. In response to environmental cues, bacteria are able to orchestrate widespread changes in mRNA lifetimes by modulating the concentration or specific activity of cellular ribonucleases or by unmasking the mRNA-degrading activity of cellular toxins.
Topics: Endoribonucleases; Escherichia coli; Gene Expression Regulation, Bacterial; Multienzyme Complexes; Phylogeny; Polyribonucleotide Nucleotidyltransferase; RNA Helicases; RNA Stability; RNA, Messenger; Ribonucleases; Ribosomes
PubMed: 25292357
DOI: 10.1146/annurev-genet-120213-092340 -
International Journal of Molecular... Dec 2017The turnover of the RNA molecules is determined by the rates of transcription and RNA degradation. Several methods have been developed to study RNA turnover since the... (Review)
Review
The turnover of the RNA molecules is determined by the rates of transcription and RNA degradation. Several methods have been developed to study RNA turnover since the beginnings of molecular biology. Here we summarize the main methods to measure RNA half-life: transcription inhibition, gene control, and metabolic labelling. These methods were used to detect the cellular activity of the mRNAs degradation machinery, including the exo-ribonuclease Xrn1 and the exosome. On the other hand, the study of the differential stability of mature RNAs has been hampered by the fact that different methods have often yielded inconsistent results. Recent advances in the systematic comparison of different method variants in yeast have permitted the identification of the least invasive methodologies that reflect half-lives the most faithfully, which is expected to open the way for a consistent quantitative analysis of the determinants of mRNA stability.
Topics: Exoribonucleases; Exosomes; Gene Expression Regulation, Fungal; Nonsense Mediated mRNA Decay; RNA Stability; RNA, Messenger; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 29244760
DOI: 10.3390/ijms18122723 -
Biological Chemistry Mar 2021RNA homeostasis is regulated by a multitude of cellular pathways. Although the addition of untemplated adenine residues to the 3' end of mRNAs has long been known to... (Review)
Review
RNA homeostasis is regulated by a multitude of cellular pathways. Although the addition of untemplated adenine residues to the 3' end of mRNAs has long been known to affect RNA stability, newly developed techniques for 3'-end sequencing of RNAs have revealed various unexpected RNA modifications. Among these, uridylation is most recognized for its role in mRNA decay but is also a key regulator of numerous RNA species, including miRNAs and tRNAs, with dual roles in both stability and maturation of miRNAs. Additionally, low levels of untemplated guanidine and cytidine residues have been observed as parts of more complex tailing patterns.
Topics: RNA; RNA Stability
PubMed: 33938180
DOI: 10.1515/hsz-2020-0325 -
Microbiological Research Mar 2018To adapt to a wide range of nutritional and environmental changes, cells must adjust their gene expression profiles. This process is completed by the frequent... (Review)
Review
To adapt to a wide range of nutritional and environmental changes, cells must adjust their gene expression profiles. This process is completed by the frequent transcription and rapid degradation of mRNA. mRNA decay is initiated by a series of endo- and exoribonucleases. These enzymes leave behind 2- to 5-nt-long oligoribonucleotides termed "nanoRNAs" that are degraded by specific nanoRNases; the degradation of nanoRNA is essential because nanoRNA can mediate the priming of transcription initiation that is harmful for the cell via an unknown mechanism. Identified nanoRNases include Orn in E. coli, NrnA and NrnB in B. subtilis, and NrnC in Bartonella. Even though these nanoRNases can degrade nanoRNA specifically into mononucleotides, the biochemical features, structural features and functional mechanisms of these enzymes are different. Sequence analysis has identified homologs of these nanoRNases in different bacteria, including Gammaproteobacteria, Betaproteobacteria, Alphaproteobacteria, Firmicutes and Cyanobacteria. However, there are several bacteria, such as those belonging to the class Thermolithobacteria, that do not have homologs of these nanoRNases. In this paper, the source of nanoRNA, the features of different kinds of nanoRNases and the distribution of these enzymes in prokaryotes are described in detail.
Topics: Bacteria; Exoribonucleases; Gene Expression Regulation, Bacterial; RNA Stability; RNA, Bacterial; RNA, Messenger; Transcription Initiation, Genetic
PubMed: 29458847
DOI: 10.1016/j.micres.2017.11.014