Deadenylation: enzymes, regulation, and functional implications

Yan, Yong-Bin

doi:10.1002/wrna.1221

Cited by 43 publications

(71 citation statements)

References 163 publications

(299 reference statements)

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“…PARN is highly conserved in higher eukaryotes, but is not identified in yeast and fly [2,4,5]. Previous functional studies have shown that PARN is involved in several crucial physiological processes such as the meiotic maturation of frog oocytes [49], embryogenesis and stress response in plants [50,51] and stage-specific protein production in Trypanosoma brucei [52].…”

Section: Discussionmentioning

confidence: 97%

“…By modulating the poly(A) tail length of mRNAs and mRNA fates thereby, deadenylases have been found to participate in many vital cellular processes such as mitotic division, oocyte maturation, differentiation and responses to various stresses [2,[4][5][6][7][8]. Whenever there is a need of metabolic changes, the fates of a certain subset of mRNAs will be regulated by either enhancing or decreasing mRNA stability.…”

Section: Introductionmentioning

confidence: 99%

“…Deadenylation is executed by deadenylases, which are a group of 3′-exoribonucleases with a high preference of poly(A) as the substrate. In most organisms, there are a number of deadenylases with distinct domain compositions and physiological functions [2,4]. According to the nature of the nuclease domain, deadenylases are divided into two classes: the endonuclease-exonuclease-phosphatase (EEP) superfamily and the DEDD/DnaQlike 3′-5′ exonuclease domain superfamily.…”

Section: Introductionmentioning

confidence: 99%

“…The EEP superfamily contains various Ccr4 orthologs and PDE12, while the Caf1 orthologs and poly(A)-specific ribonuclease (PARN) belong to the DEDD superfamily. The various deadenylases and their binding partners are evolved to endow the cell diverse methods to regulate mRNA turnover [2,4].…”

Section: Introductionmentioning

confidence: 99%

“…The number of active transcripts in the cytoplasm is determined by a number of rate-limiting steps including transcription, processing, transportation, localization, translation repression and decay [1,2]. The fate of a mature mRNA is predominantly regulated by the untranslational region (UTR) at the 5′-and 3′-end.…”

Section: Introductionmentioning

confidence: 99%

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Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

Zhang

Yan

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Regulation of mRNA decay plays a crucial role in the post-transcriptional control of cell growth, survival, differentiation, death and senescence. Deadenylation is a rate-limiting step in the silence and degradation of the bulk of highly regulated mRNAs. However, the physiological functions of various deadenylases have not been fully deciphered. In this research, we found that poly(A)-specific ribonuclease (PARN) was upregulated in gastric tumor tissues and gastric cancer cell lines MKN28 and AGS. The cellular function of PARN was investigated by stably knocking down the endogenous PARN in the MKN28 and AGS cells. Our results showed that PARN-depletion significantly inhibited the proliferation of the two types of gastric cancer cells and promoted cell death, but did not significantly affect cell motility and invasion. The depletion of PARN arrested the gastric cancer cells at the G0/G1 phase by upregulating the expression levels of p53 and p21 but not p27. The mRNA stability of p53 was unaffected by PARN-knockdown in both types of cells. A significant stabilizing effect of PARN-depletion on p21 mRNA was observed in the AGS cells but not in the MKN28 cells. We further showed that the p21 3'-UTR triggered the action of PARN in the AGS cells. The dissimilar observations between the MKN28 and AGS cells as well as various stress conditions suggested that the action of PARN strongly relied on protein expression profiles of the cells, which led to heterogeneity in the stability of PARN-targeted mRNAs.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

Zhang

Yan

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Cytoplasmic RNA Decay

Drążkowska

Tomecki

2017

Encyclopedia of Life Sciences

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RNA (ribonucleic acid) molecules play vital roles in the eukaryotic cells, not only as mediators of the flow of genetic information from DNA (deoxyribonucleic acid) to proteins but also as potent regulators of gene expression in general. Ubiquitous transcription of the eukaryotic genome, occurring in the cell nucleus, leads to the synthesis of multiple precursor RNA molecules, which undergo class‐dependent, very often complex processing events, eventually generating mature transcripts, such as mRNAs, tRNAs and rRNAs, serving as templates, adaptors and effectors, respectively, during translation. In addition, numerous noncoding RNAs (ncRNAs) are produced, which fine‐tune gene expression at different stages. Protein‐coding transcripts and many ncRNAs exert their functions in the cytoplasm. Levels of different RNA species are controlled by numerous cytoplasmic decay pathways, largely dependent on specific modifications of transcripts' ends and various enzymatic activities, including endo‐ and exoribonucleases. Moreover, RNA molecules are scrutinised for errors which may potentially impair their function by dedicated surveillance mechanisms. Key Concepts Eukaryotic genomes are almost entirely transcribed, giving rise to mRNAs, which code for proteins, and to multiple noncoding RNA classes, which impact gene expression at different levels. Posttranscriptional regulation of RNA stability represents one of the major means of controlling expression of genetic information in eukaryotes. Cytoplasm is the site of RNA decay for those transcripts which function in this subcellular compartment. Cytoplasmic mRNA decay in eukaryotes can be initiated by internal endonucleolytic cleavage or, more frequently, through digestion of nucleotides starting at the 5′‐ or the 3′‐end and carried out by 5′ to 3′ or 3′ to 5′ exoribonucleases, respectively. mRNA termini are protected by the 5′‐cap structure and (with the exception of mammalian histone‐coding transcripts) 3′ poly(A) tail with bound proteins; these protective elements are usually removed before exonucleolytic degradation. Poly(A) tail shortening (deadenylation) and extension with untemplated uridine residues (uridylation) are the most common signals triggering exonucleolytic mRNA degradation; nonpolyadenylated mRNA coding for replication‐dependent histones in mammals can also undergo uridylation, which may stimulate removal of the protective 3′ stem‐loop structure. Deadenylation or uridylation provokes cap elimination from the 5′‐end (decapping) and 5′–3′ decay by Xrn1 enzyme; alternatively, mRNA can be degraded in the opposite (3′–5′) direction by the catalytic activities associated with the multisubunit exosome complex or in an exosome‐independent pathway controlled by DIS3L2 exonuclease, stimulated by uridylation. Aberrant mRNAs, containing premature termination codons, devoid of stop codons or messengers, on which ribosomes tend to stall during translation, are removed by cytoplasmic quality control mechanisms, such as NMD, NSD and NGD. A common feature of these surveillance pathways is their dependence on ongoing protein synthesis. Notably, final phases of faulty mRNA decay in NMD/NSD/NGD are essentially carried out by the same exonucleases which control regular mRNA turnover. One of the major NMD factors is Upf1 RNA helicase, which interacts with a dimer of canonical ribosome release factors, eRF3 GTPase‐eRF1, when translation terminates on premature stop codon. On the contrary, NSD and NGD are Upf1‐independent processes, employing Ski7 GTPase‐like protein and Hbs1–Dom34 complex, structurally resembling eRF3–eRF1 dimer. Quality of some stable ncRNAs, such as tRNAs and rRNAs, can also be interrogated in the cytoplasm by dedicated surveillance mechanisms, which depend to some extent on regular and aberrant mRNA decay factors. Decay pathways for a diversified group of unstable RNA species, generated by ubiquitous transcription or untypical processing of larger molecules, are less well characterised, and for some ncRNA classes remain obscure. Depending on the organism and transcript architecture, different enzymes can be involved in removal of such transcripts from the cytoplasm of wild‐type cells. Some ncRNAs are degraded by nucleases that control mRNA fate, such as Xrn1, exosome and DIS3L2, but for other noncoding transcripts, unique cytoplasmic degradative pathways emerged during evolution.

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Connections between 3′ end processing and DNA damage response: Ten years later

Murphy

Kleiman

2019

WIREs RNA

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Ten years ago we reviewed how the cellular DNA damage response (DDR) is controlled by changes in the functional and structural properties of nuclear proteins, resulting in a timely coordinated control of gene expression that allows DNA repair. Expression of genes that play a role in DDR is regulated not only at transcriptional level during mRNA biosynthesis but also by changing steady‐state levels due to turnover of the transcripts. The 3′ end processing machinery, which is important in the regulation of mRNA stability, is involved in these gene‐specific responses to DNA damage. Here, we review the latest mechanistic connections described between 3′ end processing and DDR, with a special emphasis on alternative polyadenylation, microRNA and RNA binding proteins‐mediated deadenylation, and discuss the implications of deregulation of these steps in DDR and human disease. This article is categorized under: RNA Processing > 3′ End Processing RNA‐Based Catalysis > Miscellaneous RNA‐Catalyzed Reactions RNA in Disease and Development > RNA in Disease

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Deadenylation: enzymes, regulation, and functional implications

Cited by 43 publications

References 163 publications

Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

Cytoplasmic RNA Decay

Connections between 3′ end processing and DNA damage response: Ten years later

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