rRFtargetDB: a database of Ago1-mediated targets of ribosomal RNA fragments

Abstract

rRNA-derived fragments (rRFs) are a class of emerging posttranscriptional regulators of gene expression likely binding to the transcripts of target genes. However, the lack of knowledge about such targets hinders our understanding of rRF functions or binding mechanisms. The paucity of resources supporting the identification of the targets of rRFs creates a bottleneck in the fast-developing field. We have previously analyzed chimeric reads in cross-linked Argonaute1-RNA complexes to help infer the guide-target pairs and binding mechanisms of multiple rRFs based on experimental data in human HEK293 cells. To efficiently disseminate these results to the research community, we designed a web-based database rRFtargetDB that preserves most of the experimental results after the removal of noise and has a user-friendly interface with flexible query options and filters allowing users to obtain comprehensive information on rRFs (or targets) of interest. rRFtargetDB is populated by ∼163,000 experimentally determined unique rRF-mRNA pairs (∼60,000 supported by ≥2 reads). Almost 30,000 rRF isoforms produced >385,000 (>156,000 with ≥2 reads) chimeras with all types of RNA targets (mRNAs and noncoding RNAs). Further analyses suggested hypothetical modes of interactions, supported by secondary structures of potential guide-target hybrids and binding motifs, essential for understanding the targeting mechanisms of rRFs. All these results (ranging from the weakest to the strongest experimental support) are presented in rRFtargetDB, whose goal is to provide a resource for building users’ hypotheses on the potential roles of rRFs for experimental validation. Further, we illustrate the value/application of the database in several examples.

rRFtargetDB is freely accessible at https://grigoriev-lab.camden.rutgers.edu/tardb.