Autoantigen La Regulates MicroRNA Processing from Stem-Loop Precursors by Association with DGCR8

In humans, primary microRNA (pri-miRNA) processing starts from precise cleavage of the stem loop, which is catalyzed by the Drosha-DGCR8 complex. However, the significant inconsistencies in the expression levels among primary, precursor, and mature miRNAs clearly indicate that many other factors may be involved in this regulation. Here, we utilize a newly developed RNA affinity technique to isolate such factors. In this study, a tRNA-scaffolded aptamer (tRSA)-based RNA affinity tag, by directly fusing primary let-7 miRNA to the 3'-end of tRSA, is employed to pull down the protein components specifically binding to pri-let-7. We show that La protein binds to pri-let-7 via its La motif and significantly promotes the processing efficiency of pri-let-7 in vitro and in cells. In addition, we demonstrate that La protein is associated with DGCR8, but not Drosha, in an RNA-dependent manner. Interestingly, the RNA binding capacity of La motif is important for miRNA processing. Hence, we propose that La protein is an important microprocessor component regulating miRNA processing efficiency by association with DGCR8 to regulate formation of the DGCR8-Drosha complex for miRNA processing.