Global miRNA dosage control of embryonic germ layer specification.

ABSTRACT: MicroRNAs (miRNAs) have essential functions during embryonic development, and their dysregulation causes cancer^1,2. Altered global miRNA abundance is found in different tissues and tumours, which implies that precise control of miRNA dosage is important^1,3,4, but the underlying mechanism(s) of this control remain unknown. The protein complex Microprocessor, which comprises one DROSHA and two DGCR8 proteins, is essential for miRNA biogenesis^5-7. Here we identify a developmentally regulated miRNA dosage control mechanism that involves alternative transcription initiation (ATI) of DGCR8. ATI occurs downstream of a stem-loop in DGCR8 mRNA to bypass an autoregulatory feedback loop during mouse embryonic stem (mES) cell differentiation. Deletion of the stem-loop

SUBMITTER: Cui Y 

PROVIDER: S-EPMC8297444 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature