[
International Worm Meeting,
2021]
Regulation of gene expression is fundamental for proper development, homeostasis, and adaptation to the environment for all living organisms. Post-transcriptional gene regulation, which takes place between the transcription and the translation of a gene, is largely controlled by two classes of regulators, microRNAs (miRNAs) and RNA-binding proteins (RBPs). MiRNAs are short non-coding RNA molecules that hybridize to complementary sequences on target mRNAs, usually located in the 3'UTR region, and repress their translation or mediate their degradation. RBPs also perform their function by binding to mRNAs; however, their binding sites can be located in various regions including 5'UTRs, coding sequences, and 3'UTRs. Unlike miRNAs' repressive role, the regulatory activity of RBPs may be positive or negative, depending on the protein, the mRNA, and the biological context. In recent years, a wide repertoire of functional connections between miRNAs and RBPs has been discovered, uncovering a new level of complexity in gene expression regulation. These connections include mutual regulation of the same target mRNAs by both miRNAs and RPBs. Since both miRNAs and RBPs bind to the 3'UTR region of mRNAs, its length may add a layer of complexity to the interplay between miRNAs and RBPs. 3'UTR length is regulated by alternative polyadenylation (APA). By changing the position of polyadenylation, APA can generate transcripts with multiple 3′ UTR isoforms, each containing distinct regulatory elements (e.g., miRNA and RBP binding sites). In this study, we used C.elegans UTRome.org data that provides 3'UTR variants across different tissues, to study the coordination between miRNAs and RBPs in tissue-specific gene regulation that happens through binding to 3'UTRs. We performed a comprehensive analysis to explore regulation by individual miRNA and RBPs, as well as mutual regulation by both miRNAs and RBPs. We identified miRNA-RBP pairs that show statistically significant differential co-targeting across tissues. Our results provide evidence for complex gene regulatory networks that involve multiple factors such as miRNAs and RBPs.