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Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila

MicroRNAs (miRNAs) are 20- to ∼24-nucleotide (nt) small RNAs that impact a variety of biological processes, from development to age-associated events. To study the role of miRNAs in aging, studies have profiled the levels of miRNAs with time. However, evidence suggests that miRNAs show heterogeneity...

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Autores principales: Abe, Masashi, Naqvi, Ammar, Hendriks, Gert-Jan, Feltzin, Virzhiniya, Zhu, Yongqing, Grigoriev, Andrey, Bonini, Nancy M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894412/
https://www.ncbi.nlm.nih.gov/pubmed/24395246
http://dx.doi.org/10.1101/gad.226654.113
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author Abe, Masashi
Naqvi, Ammar
Hendriks, Gert-Jan
Feltzin, Virzhiniya
Zhu, Yongqing
Grigoriev, Andrey
Bonini, Nancy M.
author_facet Abe, Masashi
Naqvi, Ammar
Hendriks, Gert-Jan
Feltzin, Virzhiniya
Zhu, Yongqing
Grigoriev, Andrey
Bonini, Nancy M.
author_sort Abe, Masashi
collection PubMed
description MicroRNAs (miRNAs) are 20- to ∼24-nucleotide (nt) small RNAs that impact a variety of biological processes, from development to age-associated events. To study the role of miRNAs in aging, studies have profiled the levels of miRNAs with time. However, evidence suggests that miRNAs show heterogeneity in length and sequence in different biological contexts. Here, by examining the expression pattern of miRNAs by Northern blot analysis, we found that Drosophila miRNAs show distinct isoform pattern changes with age. Surprisingly, an increase of some miRNAs reflects increased 2′-O-methylation of select isoforms. Small RNA deep sequencing revealed a global increase of miRNAs loaded into Ago2, but not into Ago1, with age. Our data suggest increased loading of miRNAs into Ago2, but not Ago1, with age, indicating a mechanism for differential loading of miRNAs with age between Ago1 and Ago2. Mutations in Hen1 and Ago2, which lack 2′-O-methylation of miRNAs, result in accelerated neurodegeneration and shorter life span, suggesting a potential impact of the age-associated increase of 2′-O-methylation of small RNAs on age-associated processes. Our study highlights that miRNA 2′-O-methylation at the 3′ end is modulated by differential partitioning of miRNAs between Ago1 and Ago2 with age and that this process, along with other functions of Ago2, might impact age-associated events in Drosophila.
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spelling pubmed-38944122014-07-01 Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila Abe, Masashi Naqvi, Ammar Hendriks, Gert-Jan Feltzin, Virzhiniya Zhu, Yongqing Grigoriev, Andrey Bonini, Nancy M. Genes Dev Research Paper MicroRNAs (miRNAs) are 20- to ∼24-nucleotide (nt) small RNAs that impact a variety of biological processes, from development to age-associated events. To study the role of miRNAs in aging, studies have profiled the levels of miRNAs with time. However, evidence suggests that miRNAs show heterogeneity in length and sequence in different biological contexts. Here, by examining the expression pattern of miRNAs by Northern blot analysis, we found that Drosophila miRNAs show distinct isoform pattern changes with age. Surprisingly, an increase of some miRNAs reflects increased 2′-O-methylation of select isoforms. Small RNA deep sequencing revealed a global increase of miRNAs loaded into Ago2, but not into Ago1, with age. Our data suggest increased loading of miRNAs into Ago2, but not Ago1, with age, indicating a mechanism for differential loading of miRNAs with age between Ago1 and Ago2. Mutations in Hen1 and Ago2, which lack 2′-O-methylation of miRNAs, result in accelerated neurodegeneration and shorter life span, suggesting a potential impact of the age-associated increase of 2′-O-methylation of small RNAs on age-associated processes. Our study highlights that miRNA 2′-O-methylation at the 3′ end is modulated by differential partitioning of miRNAs between Ago1 and Ago2 with age and that this process, along with other functions of Ago2, might impact age-associated events in Drosophila. Cold Spring Harbor Laboratory Press 2014-01-01 /pmc/articles/PMC3894412/ /pubmed/24395246 http://dx.doi.org/10.1101/gad.226654.113 Text en © 2014 Abe et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ 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 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Research Paper
Abe, Masashi
Naqvi, Ammar
Hendriks, Gert-Jan
Feltzin, Virzhiniya
Zhu, Yongqing
Grigoriev, Andrey
Bonini, Nancy M.
Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila
title Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila
title_full Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila
title_fullStr Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila
title_full_unstemmed Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila
title_short Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila
title_sort impact of age-associated increase in 2′-o-methylation of mirnas on aging and neurodegeneration in drosophila
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894412/
https://www.ncbi.nlm.nih.gov/pubmed/24395246
http://dx.doi.org/10.1101/gad.226654.113
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