Structural Basis for Target-Directed MicroRNA Degradation

We used HSUR1 – a small non-coding RNA from Herpesvirus saimiri that induces degradation of host miR-27 – to validate structural insights into target-directed miRNA degradation (TDMD). While performing systematic mutagenesis of HSUR1 we noticed that HSUR1 mutants exhibiting complementarity to the extreme 3' end of miR-27, lead to generation of extended miR-27 isoforms (isomiRs). These isomiRs likely represent failed products of TDMD and could mean that features of the pairing between the TDMD target and miRNA dictate which enzymes are recruited to modify the miRNA 3′ end. Small RNA sequencing revealed that a mixture of adenylates and uridylates is added to the 3′ end of miR-27 during TDMD. miRNA-seq from BJAB cells transduced with either empty vector control or HSUR1 constructs; three biological replicates