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SnoRNA guide activities: real and ambiguous

In eukaryotes, rRNAs and spliceosomal snRNAs are heavily modified post-transcriptionally. Pseudouridylation and 2′-O-methylation are the most abundant types of RNA modifications. They are mediated by modification guide RNAs, also known as small nucleolar (sno)RNAs and small Cajal body-specific (sca)...

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Autores principales: Deryusheva, Svetlana, Talross, Gaëlle J.S., Gall, Joseph G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522698/
https://www.ncbi.nlm.nih.gov/pubmed/34385348
http://dx.doi.org/10.1261/rna.078916.121
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author Deryusheva, Svetlana
Talross, Gaëlle J.S.
Gall, Joseph G.
author_facet Deryusheva, Svetlana
Talross, Gaëlle J.S.
Gall, Joseph G.
author_sort Deryusheva, Svetlana
collection PubMed
description In eukaryotes, rRNAs and spliceosomal snRNAs are heavily modified post-transcriptionally. Pseudouridylation and 2′-O-methylation are the most abundant types of RNA modifications. They are mediated by modification guide RNAs, also known as small nucleolar (sno)RNAs and small Cajal body-specific (sca)RNAs. We used yeast and vertebrate cells to test guide activities predicted for a number of snoRNAs, based on their regions of complementarity with rRNAs. We showed that human SNORA24 is a genuine guide RNA for 18S-Ψ609, despite some noncanonical base-pairing with its target. At the same time, we found quite a few snoRNAs that have the ability to base-pair with rRNAs and can induce predicted modifications in artificial substrate RNAs, but do not modify the same target sequence within endogenous rRNA molecules. Furthermore, certain fragments of rRNAs can be modified by the endogenous yeast modification machinery when inserted into an artificial backbone RNA, even though the same sequences are not modified in endogenous yeast rRNAs. In Xenopus cells, a guide RNA generated from scaRNA, but not from snoRNA, could induce an additional pseudouridylation of U2 snRNA at position 60; both guide RNAs were equally active on a U2 snRNA-specific substrate in yeast cells. Thus, post-transcriptional modification of functionally important RNAs, such as rRNAs and snRNAs, is highly regulated and more complex than simply strong base-pairing between a guide RNA and substrate RNA. We discuss possible regulatory roles for these unexpected modifications.
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spelling pubmed-85226982021-11-01 SnoRNA guide activities: real and ambiguous Deryusheva, Svetlana Talross, Gaëlle J.S. Gall, Joseph G. RNA Article In eukaryotes, rRNAs and spliceosomal snRNAs are heavily modified post-transcriptionally. Pseudouridylation and 2′-O-methylation are the most abundant types of RNA modifications. They are mediated by modification guide RNAs, also known as small nucleolar (sno)RNAs and small Cajal body-specific (sca)RNAs. We used yeast and vertebrate cells to test guide activities predicted for a number of snoRNAs, based on their regions of complementarity with rRNAs. We showed that human SNORA24 is a genuine guide RNA for 18S-Ψ609, despite some noncanonical base-pairing with its target. At the same time, we found quite a few snoRNAs that have the ability to base-pair with rRNAs and can induce predicted modifications in artificial substrate RNAs, but do not modify the same target sequence within endogenous rRNA molecules. Furthermore, certain fragments of rRNAs can be modified by the endogenous yeast modification machinery when inserted into an artificial backbone RNA, even though the same sequences are not modified in endogenous yeast rRNAs. In Xenopus cells, a guide RNA generated from scaRNA, but not from snoRNA, could induce an additional pseudouridylation of U2 snRNA at position 60; both guide RNAs were equally active on a U2 snRNA-specific substrate in yeast cells. Thus, post-transcriptional modification of functionally important RNAs, such as rRNAs and snRNAs, is highly regulated and more complex than simply strong base-pairing between a guide RNA and substrate RNA. We discuss possible regulatory roles for these unexpected modifications. Cold Spring Harbor Laboratory Press 2021-11 /pmc/articles/PMC8522698/ /pubmed/34385348 http://dx.doi.org/10.1261/rna.078916.121 Text en © 2021 Deryusheva et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society https://creativecommons.org/licenses/by/4.0/This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Deryusheva, Svetlana
Talross, Gaëlle J.S.
Gall, Joseph G.
SnoRNA guide activities: real and ambiguous
title SnoRNA guide activities: real and ambiguous
title_full SnoRNA guide activities: real and ambiguous
title_fullStr SnoRNA guide activities: real and ambiguous
title_full_unstemmed SnoRNA guide activities: real and ambiguous
title_short SnoRNA guide activities: real and ambiguous
title_sort snorna guide activities: real and ambiguous
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522698/
https://www.ncbi.nlm.nih.gov/pubmed/34385348
http://dx.doi.org/10.1261/rna.078916.121
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