Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Karaiskos, Spyros; Naqvi, Ammar; Swanson, Karl; Grigoriev, Andrey
• Is Part Of: Biology direct. Volume 10:Issue 1(2015)
• Page Start: 1
• Page End: 13
• Publication Date: 2015-12
• Subjects: RISC -- Argonaute -- Aging -- Small RNA -- ncRNA -- tRNA -- tRF; Biology -- Periodicals; 570.5
• DOI: 10.1186/s13062-015-0081-6
• Languages: English
• ISSNs: 1745-6150

Abstract

Abstract 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 describeDrosophila 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 12Drosophila 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 thatDrosophila 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 conservedDrosophila 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.