tRFTar: Prediction of tRF-target gene interactions via systemic re-analysis of Argonaute CLIP-seq datasets

tRNA-derived fragments (tRFs), which by definition are cleaved from tRNAs, comprise a novel class of regulatory small non-coding RNAs. Recent evidence has revealed that tRFs can be loaded onto Argonaute (AGO) family proteins to perform post-transcriptional regulations via substantial tRF-target gene interactions (TGIs). However, there is no resource that systematically profiles potential AGO-mediated TGIs. To this end, we performed a systemic computational screening of potential AGO-mediated TGIs by a re-analysis of 146 crosslinkingimmunoprecipitation and high-throughput sequencing (CLIP-seq) datasets in which 920,690 TGIs between 12,102 tRFs and 5,688 target genes were identified. The predicted TGIs have superior signal-to-noise ratio and good consistency with TGIs identified from an orthogonal technique. AGO-bound tRFs are not evenly distributed, where the 5'-tRF and 3'-tRF are enriched and some commonly expressed tRFs are also overrepresented. The tRFs tend to target conserved regions of transcripts and co-express with their target genes. Filtering TGIs with consistent co-expression with target genes results in a set of regulatory TGIs that contains 25,281 tRF-target pairs. Together, our results unveiled the extensive regulatory interactions between tRFs and target genes. Finally, the CLIP-derived TGIs were incorporated in a user-friendly online platform termed as tRFTar, where various functions like custom searching, co-expressed TGI filtering, genome browser and TGI-based tRF functional enrichment analysis are enabled to help users to investigate the functions of tRFs. The tRFTar is freely available at http://www.rnanut.net/tRFTar/.

Automated summary

tRFs can be loaded onto AGO proteins for post-transcriptional regulation, and our systematic computational screening identified potential AGO-mediated TGIs with superior signal-to-noise ratio and consistency with other techniques.