Small vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencing

<p>Gene expression can be regulated by transcriptional or post-transcriptional gene silencing. Recently, we described nuclear nascent RNA silencing that is mediated by Dicer-dependent tRNA-derived small RNA molecules. In addition to tRNA, RNA polymerase III also transcribes vault RNA, a compon...

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Main Authors: Alagia, A, Tereňová, J, Ketley, RF, Di Fazio, A, Chelysheva, I, Gullerova, M
Format: Journal article
Language:English
Published: Rockefeller University Press 2023
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author Alagia, A
Tereňová, J
Ketley, RF
Di Fazio, A
Chelysheva, I
Gullerova, M
author_facet Alagia, A
Tereňová, J
Ketley, RF
Di Fazio, A
Chelysheva, I
Gullerova, M
author_sort Alagia, A
collection OXFORD
description <p>Gene expression can be regulated by transcriptional or post-transcriptional gene silencing. Recently, we described nuclear nascent RNA silencing that is mediated by Dicer-dependent tRNA-derived small RNA molecules. In addition to tRNA, RNA polymerase III also transcribes vault RNA, a component of the ribonucleoprotein complex vault. Here, we show that Dicer-dependent small vault RNA1-2 (svtRNA1-2) associates with Argonaute 2 (Ago2). Although endogenous vtRNA1-2 is present mostly in the cytoplasm, svtRNA1-2 localises predominantly in the nucleus. Furthermore, in Ago2 and Dicer knockdown cells, a subset of genes that are up-regulated at the nascent level were predicted to be targeted by svtRNA1-2 in the intronic region. Genomic deletion of vtRNA1-2 results in impaired cellular proliferation and the up-regulation of genes associated with cell membrane physiology and cell adhesion. Silencing activity of svtRNA1-2 molecules is dependent on seed-plus-complementary-paired hybridisation features and the presence of a 5-nucleotide loop protrusion on target RNAs. Our data reveal a role of Dicer-dependent svtRNA1-2, possessing unique molecular features, in modulation of the expression of membrane-associated proteins at the nascent RNA level.</p>
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spelling oxford-uuid:c655fdc9-3574-4635-9733-519b78bc04a12023-07-21T11:48:34ZSmall vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c655fdc9-3574-4635-9733-519b78bc04a1EnglishSymplectic ElementsRockefeller University Press 2023Alagia, ATereňová, JKetley, RFDi Fazio, AChelysheva, IGullerova, M<p>Gene expression can be regulated by transcriptional or post-transcriptional gene silencing. Recently, we described nuclear nascent RNA silencing that is mediated by Dicer-dependent tRNA-derived small RNA molecules. In addition to tRNA, RNA polymerase III also transcribes vault RNA, a component of the ribonucleoprotein complex vault. Here, we show that Dicer-dependent small vault RNA1-2 (svtRNA1-2) associates with Argonaute 2 (Ago2). Although endogenous vtRNA1-2 is present mostly in the cytoplasm, svtRNA1-2 localises predominantly in the nucleus. Furthermore, in Ago2 and Dicer knockdown cells, a subset of genes that are up-regulated at the nascent level were predicted to be targeted by svtRNA1-2 in the intronic region. Genomic deletion of vtRNA1-2 results in impaired cellular proliferation and the up-regulation of genes associated with cell membrane physiology and cell adhesion. Silencing activity of svtRNA1-2 molecules is dependent on seed-plus-complementary-paired hybridisation features and the presence of a 5-nucleotide loop protrusion on target RNAs. Our data reveal a role of Dicer-dependent svtRNA1-2, possessing unique molecular features, in modulation of the expression of membrane-associated proteins at the nascent RNA level.</p>
spellingShingle Alagia, A
Tereňová, J
Ketley, RF
Di Fazio, A
Chelysheva, I
Gullerova, M
Small vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencing
title Small vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencing
title_full Small vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencing
title_fullStr Small vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencing
title_full_unstemmed Small vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencing
title_short Small vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencing
title_sort small vault rna1 2 modulates expression of cell membrane proteins through nascent rna silencing
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