Description
The precise control of microRNA (miRNA) biogenesis is important for various cellular functions, and its dysregulation is often associated with human diseases. We previously reported that Terminal uridylyl transferase 4 (TUT4) down-regulates let-7 miRNA biogenesis by oligo-uridylating let-7 precursor (pre-let-7) in mouse embryonic stem cells and that a pluripotency marker Lin28 promotes a processivity of TUT4. Here we find that TUT4 positively controls let-7 biogenesis by adding a uridine residue to the 3' end of pre-let-7 in the absence of Lin28. Such mono-uridylation enhances Dicer processing by generating an optimal end structure of pre-let-7 for Dicer recognition and may protect pre-miRNA from trimming. Moreover, TUT7, TUT4 and TUT2 redundantly regulate pre-let-7 processing and simultaneous knock down of these TUTs leads to the decrease of mature let-7 and the accumulation of pre-let-7 in cells. This study provides a novel regulation mechanism of miRNA biogenesis, which may function in development and tumorigenesis. Overall design: HeLa cells were transfected with siRNA two times over a 4~5 day period.