Background: Accumulating evidence points to the functional roles of rRNA derived
Fragments (rRFs), often considered degradation byproducts. Small RNAs, including miRNAs and
tRNA-derived Fragments (tRFs), have been implicated in the aging process and we considered rRFs
in this context.
Objective: We performed a computational analysis of Argonaute-loaded rRFs in Drosophila melanogaster
to study rRF changes with age. We determined rRF abundance in Ago1 and Ago2 at 3 and 30
days to identify Ago1-guided and Ago2-guided fragments. We searched for putative seed sequences
in rRFs based on frequent matches of sliding k-mer windows to the conserved regions of 12 Drosophila
genomes. We predicted putative targets (containing matches to seeds identified in four rRFs)
and studied their functional enrichments using Gene Ontology.
Results: We identified precise cleavage sites of distinct rRF isoforms from both nuclear and mitochondrial
rRNAs. The most prominent rRF isoforms were enriched in Ago2 at 3 days and that loading
strongly decreased with age. For less abundant rRFs, loading of Ago2-guided rRFs generally increased
in Ago2, whereas Ago1-guided rRFs revealed diverse patterns. The distribution of seed
matches in targets suggested that rRFs may bind to various conserved regions of many genes, possibly
via miRNA-like seed-based mechanisms.
Conclusion: Our observations suggest that rRFs may be functional molecules, with age-dependent
Argonaute loading, comparable to that of miRNAs and tRFs. The putative rRF targets showed significant
enrichment in developmental processes and biological regulation, similar to tRFs and consistent
with a possible involvement of these newly identified small RNAs in the Drosophila aging.