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Mechanistic insights into non-coding Y RNA processing
Y RNAs (84–112 nt) are non-coding RNAs transcribed by RNA polymerase III and are characterized by a distinctive secondary structure. Human Y RNAs interact with the autoimmune proteins SSB and RO60 that together form a ribonucleoprotein (RNP) complex termed RoRNP and Y RNAs also perform regulatory ro...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973356/ https://www.ncbi.nlm.nih.gov/pubmed/35354369 http://dx.doi.org/10.1080/15476286.2022.2057725 |
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author | Billmeier, Martina Green, Darrell Hall, Adam E. Turnbull, Carly Singh, Archana Xu, Ping Moxon, Simon Dalmay, Tamas |
author_facet | Billmeier, Martina Green, Darrell Hall, Adam E. Turnbull, Carly Singh, Archana Xu, Ping Moxon, Simon Dalmay, Tamas |
author_sort | Billmeier, Martina |
collection | PubMed |
description | Y RNAs (84–112 nt) are non-coding RNAs transcribed by RNA polymerase III and are characterized by a distinctive secondary structure. Human Y RNAs interact with the autoimmune proteins SSB and RO60 that together form a ribonucleoprotein (RNP) complex termed RoRNP and Y RNAs also perform regulatory roles in DNA and RNA replication and stability, which has major implications for diseases including cancer. During cellular stress and apoptosis, Y RNAs are cleaved into 3’ and 5’ end fragments termed Y RNA-derived small RNAs (ysRNAs). Although some ysRNA functions in stress, apoptosis and cancer have been reported, their fundamental biogenesis has not been described. Here we report that 3’ end RNY5 cleavage is structure dependent. In high throughput mutagenesis experiments, cleavage occurred between the 2(nd) and 3(rd) nt above a double stranded stem comprising high GC content. We demonstrate that an internal loop above stem S3 is critical for producing 3’ end ysRNAs (31 nt) with mutants resulting in longer or no ysRNAs. We show a UGGGU sequence motif at position 22 of RNY5 is critical for producing 5’ end ysRNAs (22–25 nt). We show that intact RO60 is critical for ysRNA biogenesis. We conclude that ribonuclease L (RNASEL) contributes to Y RNA cleavage in mouse embryonic fibroblasts but is not the only endoribonuclease important in human cells. |
format | Online Article Text |
id | pubmed-8973356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-89733562022-04-02 Mechanistic insights into non-coding Y RNA processing Billmeier, Martina Green, Darrell Hall, Adam E. Turnbull, Carly Singh, Archana Xu, Ping Moxon, Simon Dalmay, Tamas RNA Biol Research Paper Y RNAs (84–112 nt) are non-coding RNAs transcribed by RNA polymerase III and are characterized by a distinctive secondary structure. Human Y RNAs interact with the autoimmune proteins SSB and RO60 that together form a ribonucleoprotein (RNP) complex termed RoRNP and Y RNAs also perform regulatory roles in DNA and RNA replication and stability, which has major implications for diseases including cancer. During cellular stress and apoptosis, Y RNAs are cleaved into 3’ and 5’ end fragments termed Y RNA-derived small RNAs (ysRNAs). Although some ysRNA functions in stress, apoptosis and cancer have been reported, their fundamental biogenesis has not been described. Here we report that 3’ end RNY5 cleavage is structure dependent. In high throughput mutagenesis experiments, cleavage occurred between the 2(nd) and 3(rd) nt above a double stranded stem comprising high GC content. We demonstrate that an internal loop above stem S3 is critical for producing 3’ end ysRNAs (31 nt) with mutants resulting in longer or no ysRNAs. We show a UGGGU sequence motif at position 22 of RNY5 is critical for producing 5’ end ysRNAs (22–25 nt). We show that intact RO60 is critical for ysRNA biogenesis. We conclude that ribonuclease L (RNASEL) contributes to Y RNA cleavage in mouse embryonic fibroblasts but is not the only endoribonuclease important in human cells. Taylor & Francis 2022-03-30 /pmc/articles/PMC8973356/ /pubmed/35354369 http://dx.doi.org/10.1080/15476286.2022.2057725 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Billmeier, Martina Green, Darrell Hall, Adam E. Turnbull, Carly Singh, Archana Xu, Ping Moxon, Simon Dalmay, Tamas Mechanistic insights into non-coding Y RNA processing |
title | Mechanistic insights into non-coding Y RNA processing |
title_full | Mechanistic insights into non-coding Y RNA processing |
title_fullStr | Mechanistic insights into non-coding Y RNA processing |
title_full_unstemmed | Mechanistic insights into non-coding Y RNA processing |
title_short | Mechanistic insights into non-coding Y RNA processing |
title_sort | mechanistic insights into non-coding y rna processing |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973356/ https://www.ncbi.nlm.nih.gov/pubmed/35354369 http://dx.doi.org/10.1080/15476286.2022.2057725 |
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