Abstract
Background:The progress of next-generation sequencing technologies has unveiled various non-coding RNAs that have previously been considered products of random degradation and attracted only minimal interest. Among small RNA families, microRNA (miRNAs) have traditionally been considered key post-transcriptional regulators. However, recent studies have reported evidence for widespread presence of fragments of tRNA molecules (tRFs) across a range of organisms and tissues, and of tRF involvement in Argonaute complexes. Methods:To elucidate potential tRF functionality, we compared available RNA sequencing datasets derived from the brains of young, mid-aged and old rats. Using sliding 7-mer windows along a tRF, we searched for putative seed sequences with high numbers of conserved complementary sites within 3' UTRs of 23 vertebrate genomes. We analyzed Gene Ontology term enrichment of predicted tRF targets and compared their transcript levels with targets of miRNAs in the context of age. Results and Discussion:We detected tRFs originating from 3'- and 5'-ends of tRNAs in rat brains at significant levels. These fragments showed dynamic changes: 3' tRFs monotonously increased with age, while 5' tRFs displayed less consistent patterns. Furthermore, 3' tRFs showed a narrow size range compared to 5' tRFs, suggesting a difference in their biogenesis mechanisms. Similar to our earlier results in Drosophila and compatible with other experimental findings, we found "seed" sequence locations on both ends of different tRFs. Putative targets of these fragments were found to be enriched in neuronal and developmental functions. Comparison of tRFs and miRNAs increasing in abundance with age revealed small, but distinct changes in brain target transcript levels for these two types of small RNA, with the higher proportion of tRF targets decreasing with age. We also illustrated the utility of tRF analysis for annotating tRNA genes in sequenced genomes.
Highlights
Small RNA molecules derived from fragmented tRNAs form a new class of short (~16–40 nt) RNA molecules
Results and discussion tRNA fragments in rat brain We analyzed available datasets of nine different small-RNA libraries corresponding to three replicates for three distinct time points throughout a rat lifespan
After mapping short RNA reads from these libraries to the union of tRNA sequences obtained from two independent databases, we observed that the vast majority of alignments localized preferentially to a 5’- or a 3’-end of a tRNA molecule
Summary
Small RNA molecules derived from fragmented tRNAs form a new class of short (~16–40 nt) RNA molecules They arise from directed cleavage of cellular tRNAs, including both tRNA precursor species, as well as mature, functional tRNA molecules, and have been associated with multiple infectious diseases, pathogen resistance and regulation[1,2]. Results and Discussion: We detected tRFs originating from 3’- and 5’-ends of tRNAs in rat brains at significant levels. These fragments showed dynamic changes: 3’ tRFs monotonously increased with age, while 5’ tRFs displayed less consistent patterns. We illustrated the utility of tRF analysis for annotating tRNA genes in sequenced genomes
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