Regulation of RNA stability at the 3′ end

Frederick, Mallory I.; Heinemann, Ilka U.

doi:10.1515/hsz-2020-0325

Cited by 16 publications

(14 citation statements)

References 46 publications

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“…The most important conclusion of the work presented here is that phosphorylation of Puf1 and Puf2 by the protein kinase Ypk1 is yet another mechanism by which the TORC2-Ypk1 signaling axis controls the composition and function of the PM. In this sense, the regulatory circuitry we have described here joins a growing list of examples which illustrate that phosphorylation is a widely used means for regulating the function of Puf family members [ 87 , 89 , 90 ] and other classes of mRNA-binding proteins [ 91 , 92 , 93 ].…”

Section: Discussionmentioning

confidence: 96%

Phosphorylation of mRNA-Binding Proteins Puf1 and Puf2 by TORC2-Activated Protein Kinase Ypk1 Alleviates Their Repressive Effects

et al. 2021

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Members of the Puf family of RNA-binding proteins typically associate via their Pumilio homology domain with specific short motifs in the 3’-UTR of an mRNA and thereby influence the stability, localization and/or efficiency of translation of the bound transcript. In our prior unbiased proteome-wide screen for targets of the TORC2-stimulated protein kinase Ypk1, we identified the paralogs Puf1/Jsn1 and Puf2 as high-confidence substrates. Earlier work by others had demonstrated that Puf1 and Puf2 exhibit a marked preference for interaction with mRNAs encoding plasma membrane-associated proteins, consistent with our previous studies documenting that a primary physiological role of TORC2-Ypk1 signaling is maintenance of plasma membrane homeostasis. Here, we show, first, that both Puf1 and Puf2 are authentic Ypk1 substrates both in vitro and in vivo. Fluorescently tagged Puf1 localizes constitutively in cortical puncta closely apposed to the plasma membrane, whereas Puf2 does so in the absence of its Ypk1 phosphorylation, but is dispersed in the cytosol when phosphorylated. We further demonstrate that Ypk1-mediated phosphorylation of Puf1 and Puf2 upregulates production of the protein products of the transcripts to which they bind, with a concomitant increase in the level of the cognate mRNAs. Thus, Ypk1 phosphorylation relieves Puf1- and Puf2-mediated post-transcriptional repression mainly by counteracting their negative effect on transcript stability. Using a heterologous protein-RNA tethering and fluorescent protein reporter assay, the consequence of Ypk1 phosphorylation in vivo was recapitulated for full-length Puf1 and even for N-terminal fragments (residues 1-340 and 143-295) corresponding to the region upstream of its dimerization domain (an RNA-recognition motif fold) encompassing its two Ypk1 phosphorylation sites (both also conserved in Puf2). This latter result suggests that alleviation of Puf1-imposed transcript destabilization does not obligatorily require dissociation of Ypk1-phosphorylated Puf1 from a transcript. Our findings add new insight about how the TORC2-Ypk1 signaling axis regulates the content of plasma membrane-associated proteins to promote maintenance of the integrity of the cell envelope.

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Section: Discussionmentioning

confidence: 96%

Phosphorylation of mRNA-Binding Proteins Puf1 and Puf2 by TORC2-Activated Protein Kinase Ypk1 Alleviates Their Repressive Effects

et al. 2021

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“…Аденілірування мікроРНК найчастіше сприяє стабілізації молекули, але в деяких випадках може призвести і до деградації мікроРНК [11,15,35]. Результати геномного аналізу свідчать про те, що основним аденіліруючим ферментом для широкого спектра мікроРНК є цитоплазматична полі(А)-термінальна нуклеотидилтрансфераза 2 (terminal nucleotidyltransferase 2 -TENT2) [3,9]. Так, ефект стабілізації молекули мікроРНК, що обумовлений аденіліруванням, продемонстрований на прикладі молекули miR-122.…”

Section: рисунок 4 модель стабілізації молекули Mir-122 за рахунок аденілірування 3'-кінця [11] примітка: у цитоплазмі Pre-mir-122 за допunclassified

“…Деаденілірування miR-122 виконується полі(А)специфічною рибонуклеазою (poly-(A)-specific ribonuclease -PARN) (рис. 4) [9,11,12].…”

Regulation of miRNA content. Part 1. Editing miRNA. Тailing miRNA

Абатуров¹,

Babуch²

2022

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This scientific review presents the processes of regulation of miRNA content. To write the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka databases. The article presents the characteristics of the processes of microRNA editing and microRNA tailing, which regulate the content of microRNA through the transcription control. It is emphasized that editing is the most important mechanism of posttranscriptional regulation of microRNA that occurs with the help of RNA-specific adenosine deaminase. The article shows that editing leads to a change in the secondary structure of the microRNA molecule and the deviation of the process of microRNA maturation. It is shown that microRNA tailing is a posttranscriptional elongation of the tail of the molecule by adding nucleotides to the 3’-end of RNA. It has been found that uridinylation is a very common posttranscriptional process that regulates gene expression. The effect of uridinylation on microRNA biogenesis has been demonstrated on the example of the miR let-7 family, which inhibits proliferation and promotes cell differentiation. It has been established that another type of microRNA tailing, namely adenylation, most often contributes to the stabilization of the molecule, but in some cases can lead to microRNA degradation. Thus, the regulation of miRNA content is carried out by editing miRNA, microRNA tailing. Due to editing, the secondary structure of the microRNA molecule changes and the microRNA maturation process deviates. MicroRNA tailing is a post-transcriptional elongation of the tail of the molecule by adding nucleotides to the 3’-end of RNA by polyuridinylation or polyadenylation. Uridinylation affects the processing and degradation of miRNA precursors with different molecular effects, which in some cases contribute to the development of diseases.

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“…Усередині комплексу Exo9 проходить центральний канал з трьома каталітичними центрами, який приймає молекулу РНК (рис. 3) [8,[10][11][12]16].…”

Section: рисунок 1 вплив Xrn екзорибонуклеаз на стабільність зрілих форм мікрорнк [36] примітки: 1) зрілі мікрорнк можуть бути деградованunclassified

Regulation of miRNA content. Part 2. Degradation of miRNAs

Абатуров¹,

Babуch²

2022

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The scientific review presents the process of regulation of microRNA content — microRNA degradation. To write the article, information was searched using databases Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka. The article presents the characteristics of the most important process of RNA metabolism — degradation of 3'→5' RNA. Degradation of microRNA is inherent in organisms of all kingdoms of life and is involved in the regulation of RNA representation, elimination of dysfunctional or incorrectly constructed RNA molecules and processing of RNA precursors. Exoribonucleases that affect the stability of mature forms of miRNA are presented. It is emphasized that XRN exoribonucleases degrade various RNA substrates during total RNA degradation and are involved in specific processes such as nonsense-mediated degradation, gene silencing, rRNA maturation, and transcription termination. It is shown that exoribonuclease XRN2 plays a crucial role in the termination of transcription during viral infection, namely it has cytoplasmic antiviral activity against hepatitis C virus. The role of RNA-degrading exosome in microRNA degradation is presented. RNA-degrading exosome is a ubiquitous complex and 3'-5'-endo- and exoribonucleases of eukaryotes, which interacts with several processing cofactors and degrades almost all classes of cytoplasmic RNA. The article reflects the function of evolutionarily conserved phosphorolytic 3'-5'-exoribonuclease — polynucleotide phosphorylase. The role of exoribonuclease 1, which is an evolutionarily conserved 3'-5'-exoribonuclease of the DEDDh family, is involved in the final processing of 5.8S rRNA, replication-dependent histone mRNA, siRNA, and miRNA. Eri1 exoribonuclease has been shown to regulate global microRNA homeostasis in lymphocytes and to participate in NK cell development and antiviral response. Thus, one of the mechanisms of regulation of miRNA content is the most important process of RNA metabolism, which is inherent in organisms of all kingdoms of life, namely the degradation of miRNAs.

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Regulation of RNA stability at the 3′ end

Cited by 16 publications

References 46 publications

Phosphorylation of mRNA-Binding Proteins Puf1 and Puf2 by TORC2-Activated Protein Kinase Ypk1 Alleviates Their Repressive Effects

Phosphorylation of mRNA-Binding Proteins Puf1 and Puf2 by TORC2-Activated Protein Kinase Ypk1 Alleviates Their Repressive Effects

Regulation of miRNA content. Part 1. Editing miRNA. Тailing miRNA

Regulation of miRNA content. Part 2. Degradation of miRNAs

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