Modulation of microRNA processing by mismatch repair protein MutLa

MicroRNAs （miRNAs） are critical post-transcriptional regulators and are derived from hairpin-snaped primary transcripts via a series of processing steps. However, how the production of individual miRNAs is regulated remains largely unknown. Similarly, loss or overexpression of the key mismatch repair protein MutLa （MLH1-PMS2 heterodimer） leads to genome instability and tumorigenesis, but the mechanisms controlling MutLa expression are unknown. Here we demonstrate in vitro and in vivo that MLH1 and miR-422a participate in a feedback loop that regulates the level of both molecules. Using a defined in-vitro miRNA processing system, we show that MutLa stimulates the conversion of pri-miRo422a to pre-miR-422a, as well as the processing of other miRNAs tested,