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Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets
BACKGROUND: Development of sequencing technologies and supporting computation enable discovery of small RNA molecules that previously escaped detection or were ignored due to low count numbers. While the focus in the analysis of small RNA libraries has been primarily on microRNAs (miRNAs), recent st...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572633/ https://www.ncbi.nlm.nih.gov/pubmed/26374501 http://dx.doi.org/10.1186/s13062-015-0081-6 |
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author | Karaiskos, Spyros Naqvi, Ammar S. Swanson, Karl E. Grigoriev, Andrey |
author_facet | Karaiskos, Spyros Naqvi, Ammar S. Swanson, Karl E. Grigoriev, Andrey |
author_sort | Karaiskos, Spyros |
collection | PubMed |
description | BACKGROUND: Development of sequencing technologies and supporting computation enable discovery of small RNA molecules that previously escaped detection or were ignored due to low count numbers. While the focus in the analysis of small RNA libraries has been primarily on microRNAs (miRNAs), recent studies have reported findings of fragments of transfer RNAs (tRFs) across a range of organisms. RESULTS: Here we describe Drosophila melanogaster tRFs, which appear to have a number of structural and functional features similar to those of miRNAs but are less abundant. As is the case with miRNAs, (i) tRFs seem to have distinct isoforms preferentially originating from 5’ or 3’ end of a precursor molecule (in this case, tRNA), (ii) ends of tRFs appear to contain short “seed” sequences matching conserved regions across 12 Drosophila genomes, preferentially in 3’ UTRs but also in introns and exons; (iii) tRFs display specific isoform loading into Ago1 and Ago2 and thus likely function in RISC complexes; (iii) levels of loading in Ago1 and Ago2 differ considerably; and (iv) both tRF expression and loading appear to be age-dependent, indicating potential regulatory changes from young to adult organisms. CONCLUSIONS: We found that Drosophila tRF reads mapped to both nuclear and mitochondrial tRNA genes for all 20 amino acids, while previous studies have usually reported fragments from only a few tRNAs. These tRFs show a number of similarities with miRNAs, including seed sequences. Based on complementarity with conserved Drosophila regions we identified such seed sequences and their possible targets with matches in the 3’UTR regions. Strikingly, the potential target genes of the most abundant tRFs show significant Gene Ontology enrichment in development and neuronal function. The latter suggests that involvement of tRFs in the RNA interfering pathway may play a role in brain activity or brain changes with age. REVIEWERS: This article was reviewed by Eugene Koonin, Neil Smalheiser and Alexander Kel. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13062-015-0081-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4572633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45726332015-09-18 Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets Karaiskos, Spyros Naqvi, Ammar S. Swanson, Karl E. Grigoriev, Andrey Biol Direct Research BACKGROUND: Development of sequencing technologies and supporting computation enable discovery of small RNA molecules that previously escaped detection or were ignored due to low count numbers. While the focus in the analysis of small RNA libraries has been primarily on microRNAs (miRNAs), recent studies have reported findings of fragments of transfer RNAs (tRFs) across a range of organisms. RESULTS: Here we describe Drosophila melanogaster tRFs, which appear to have a number of structural and functional features similar to those of miRNAs but are less abundant. As is the case with miRNAs, (i) tRFs seem to have distinct isoforms preferentially originating from 5’ or 3’ end of a precursor molecule (in this case, tRNA), (ii) ends of tRFs appear to contain short “seed” sequences matching conserved regions across 12 Drosophila genomes, preferentially in 3’ UTRs but also in introns and exons; (iii) tRFs display specific isoform loading into Ago1 and Ago2 and thus likely function in RISC complexes; (iii) levels of loading in Ago1 and Ago2 differ considerably; and (iv) both tRF expression and loading appear to be age-dependent, indicating potential regulatory changes from young to adult organisms. CONCLUSIONS: We found that Drosophila tRF reads mapped to both nuclear and mitochondrial tRNA genes for all 20 amino acids, while previous studies have usually reported fragments from only a few tRNAs. These tRFs show a number of similarities with miRNAs, including seed sequences. Based on complementarity with conserved Drosophila regions we identified such seed sequences and their possible targets with matches in the 3’UTR regions. Strikingly, the potential target genes of the most abundant tRFs show significant Gene Ontology enrichment in development and neuronal function. The latter suggests that involvement of tRFs in the RNA interfering pathway may play a role in brain activity or brain changes with age. REVIEWERS: This article was reviewed by Eugene Koonin, Neil Smalheiser and Alexander Kel. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13062-015-0081-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-16 /pmc/articles/PMC4572633/ /pubmed/26374501 http://dx.doi.org/10.1186/s13062-015-0081-6 Text en © Karaiskos et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Karaiskos, Spyros Naqvi, Ammar S. Swanson, Karl E. Grigoriev, Andrey Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets |
title | Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets |
title_full | Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets |
title_fullStr | Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets |
title_full_unstemmed | Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets |
title_short | Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets |
title_sort | age-driven modulation of trna-derived fragments in drosophila and their potential targets |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572633/ https://www.ncbi.nlm.nih.gov/pubmed/26374501 http://dx.doi.org/10.1186/s13062-015-0081-6 |
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