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A microRNA feedback loop regulates global microRNA abundance during aging
Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcrip...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769744/ https://www.ncbi.nlm.nih.gov/pubmed/29114017 http://dx.doi.org/10.1261/rna.062190.117 |
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author | Inukai, Sachi Pincus, Zachary de Lencastre, Alexandre Slack, Frank J. |
author_facet | Inukai, Sachi Pincus, Zachary de Lencastre, Alexandre Slack, Frank J. |
author_sort | Inukai, Sachi |
collection | PubMed |
description | Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline. |
format | Online Article Text |
id | pubmed-5769744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57697442019-02-01 A microRNA feedback loop regulates global microRNA abundance during aging Inukai, Sachi Pincus, Zachary de Lencastre, Alexandre Slack, Frank J. RNA Article Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline. Cold Spring Harbor Laboratory Press 2018-02 /pmc/articles/PMC5769744/ /pubmed/29114017 http://dx.doi.org/10.1261/rna.062190.117 Text en © 2018 Inukai et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 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/. |
spellingShingle | Article Inukai, Sachi Pincus, Zachary de Lencastre, Alexandre Slack, Frank J. A microRNA feedback loop regulates global microRNA abundance during aging |
title | A microRNA feedback loop regulates global microRNA abundance during aging |
title_full | A microRNA feedback loop regulates global microRNA abundance during aging |
title_fullStr | A microRNA feedback loop regulates global microRNA abundance during aging |
title_full_unstemmed | A microRNA feedback loop regulates global microRNA abundance during aging |
title_short | A microRNA feedback loop regulates global microRNA abundance during aging |
title_sort | microrna feedback loop regulates global microrna abundance during aging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769744/ https://www.ncbi.nlm.nih.gov/pubmed/29114017 http://dx.doi.org/10.1261/rna.062190.117 |
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