Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins

ABSTRACT: Binding of microRNAs (miRNA) to mRNAs normally results in post-transcriptional repression. However, extensive base-pairing between miRNAs and target RNAs can trigger miRNA degradation, a phenomenon called target RNA-directed miRNA degradation (TDMD). Here, we systematically analyzed Argonaute-CLASH (crosslinking, ligation, and sequencing of miRNA-target RNA hybrids) data, and identified numerous candidate TDMD triggers based on their ability to induce non-templated nucleotide addition at the miRNA 3 end. When overexpressed in HEK293T cells, nine highly conserved triggers induce degradation of corresponding miRNAs. Consistent with previous reports, both the TDMD base-pairing and surrounding sequences are important for TDMD. CRISPR knockout of endogenous trigger or ZSWIM8, a ubiquitin ligase essential for TDMD, reduce miRNA degradation. Furthermore, degradation of miR-221 and miR-222 by a trigger in BCL2L11, which encodes an apoptotic protein, enhances apoptosis. Therefore, we uncovered widespread TDMD triggers in target RNAs and demonstrated that they can functionally cooperate with the encoded proteins.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178943 | GEO | 2024/06/25

REPOSITORIES: GEO