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Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins

Binding of microRNAs (miRNAs) to mRNAs normally results in post-transcriptional repression of gene expression. However, extensive base-pairing between miRNAs and target RNAs can trigger miRNA degradation, a phenomenon called target RNA-directed miRNA degradation (TDMD). Here, we systematically analy...

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Autores principales: Li, Lu, Sheng, Peike, Li, Tianqi, Fields, Christopher J., Hiers, Nicholas M., Wang, Yuzhi, Li, Jianping, Guardia, Casey M., Licht, Jonathan D., Xie, Mingyi
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/PMC8653786/
https://www.ncbi.nlm.nih.gov/pubmed/34819352
http://dx.doi.org/10.1101/gad.348874.121
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author Li, Lu
Sheng, Peike
Li, Tianqi
Fields, Christopher J.
Hiers, Nicholas M.
Wang, Yuzhi
Li, Jianping
Guardia, Casey M.
Licht, Jonathan D.
Xie, Mingyi
author_facet Li, Lu
Sheng, Peike
Li, Tianqi
Fields, Christopher J.
Hiers, Nicholas M.
Wang, Yuzhi
Li, Jianping
Guardia, Casey M.
Licht, Jonathan D.
Xie, Mingyi
author_sort Li, Lu
collection PubMed
description Binding of microRNAs (miRNAs) to mRNAs normally results in post-transcriptional repression of gene expression. However, extensive base-pairing between miRNAs and target RNAs can trigger miRNA degradation, a phenomenon called target RNA-directed miRNA degradation (TDMD). Here, we systematically analyzed Argonaute-CLASH (cross-linking, ligation, and sequencing of miRNA–target RNA hybrids) data and identified numerous candidate TDMD triggers, focusing on their ability to induce nontemplated nucleotide addition at the miRNA 3′ end. When exogenously expressed in various cell lines, eight triggers induce degradation of corresponding miRNAs. Both the TDMD base-pairing and surrounding sequences are essential for TDMD. CRISPR knockout of endogenous trigger or ZSWIM8, a ubiquitin ligase essential for TDMD, reduced miRNA degradation. Furthermore, degradation of miR-221 and miR-222 by a trigger in BCL2L11, which encodes a proapoptotic protein, enhances apoptosis. Therefore, we uncovered widespread TDMD triggers in target RNAs and demonstrated an example that could functionally cooperate with the encoded protein.
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spelling pubmed-86537862022-06-01 Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins Li, Lu Sheng, Peike Li, Tianqi Fields, Christopher J. Hiers, Nicholas M. Wang, Yuzhi Li, Jianping Guardia, Casey M. Licht, Jonathan D. Xie, Mingyi Genes Dev Research Paper Binding of microRNAs (miRNAs) to mRNAs normally results in post-transcriptional repression of gene expression. However, extensive base-pairing between miRNAs and target RNAs can trigger miRNA degradation, a phenomenon called target RNA-directed miRNA degradation (TDMD). Here, we systematically analyzed Argonaute-CLASH (cross-linking, ligation, and sequencing of miRNA–target RNA hybrids) data and identified numerous candidate TDMD triggers, focusing on their ability to induce nontemplated nucleotide addition at the miRNA 3′ end. When exogenously expressed in various cell lines, eight triggers induce degradation of corresponding miRNAs. Both the TDMD base-pairing and surrounding sequences are essential for TDMD. CRISPR knockout of endogenous trigger or ZSWIM8, a ubiquitin ligase essential for TDMD, reduced miRNA degradation. Furthermore, degradation of miR-221 and miR-222 by a trigger in BCL2L11, which encodes a proapoptotic protein, enhances apoptosis. Therefore, we uncovered widespread TDMD triggers in target RNAs and demonstrated an example that could functionally cooperate with the encoded protein. Cold Spring Harbor Laboratory Press 2021-12-01 /pmc/articles/PMC8653786/ /pubmed/34819352 http://dx.doi.org/10.1101/gad.348874.121 Text en © 2021 Li et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Research Paper
Li, Lu
Sheng, Peike
Li, Tianqi
Fields, Christopher J.
Hiers, Nicholas M.
Wang, Yuzhi
Li, Jianping
Guardia, Casey M.
Licht, Jonathan D.
Xie, Mingyi
Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins
title Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins
title_full Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins
title_fullStr Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins
title_full_unstemmed Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins
title_short Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins
title_sort widespread microrna degradation elements in target mrnas can assist the encoded proteins
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653786/
https://www.ncbi.nlm.nih.gov/pubmed/34819352
http://dx.doi.org/10.1101/gad.348874.121
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