title: Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets.
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 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.
authors.affiliation: Department of BiologyCenter for Computational and Integrative Biology, Rutgers University, Camden, NJ, 08102, USA. spyros.karaiskos@rutgers.edu.
authors.forename: Spyros
authors.initials: S
authors.lastname: Karaiskos
authors.affiliation: Department of BiologyCenter for Computational and Integrative Biology, Rutgers University, Camden, NJ, 08102, USA. ammar.naqvi@rutgers.edu.
authors.forename: Ammar S
authors.initials: AS
authors.lastname: Naqvi
authors.affiliation: Department of BiologyCenter for Computational and Integrative Biology, Rutgers University, Camden, NJ, 08102, USA. kswanson@rutgers.edu.
authors.forename: Karl E
authors.initials: KE
authors.lastname: Swanson
authors.affiliation: Department of BiologyCenter for Computational and Integrative Biology, Rutgers University, Camden, NJ, 08102, USA. andrey.grigoriev@rutgers.edu.
authors.forename: Andrey
authors.initials: A
authors.lastname: Grigoriev
mesh_terms: D000375:Aging; D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D006824:Hybridization, Genetic; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012343:RNA, Transfer