An intrinsically disordered region of Drosha selectively promotes miRNA biogenesis, independent of tissue-specific Microprocessor condensates
Precise control of miRNA biogenesis is of extreme importance, since mis-regulation of miRNAs underlies or exacerbates many disease states. The Microprocessor complex, composed of DROSHA and DGCR8, carries out the first of two cleavage steps in canonical miRNA biogenesis. Despite recent advances in understanding the molecular mechanism of Microprocessor, the role of N-terminal regions of DROSHA is less characterized due their high intrinsic disorder. Here we demonstrate that Microprocessor forms liquid-liquid phase separated (LLPS) condensates in select tissues in C. elegans.  We find that an intrinsically disordered region (IDR) near the N-terminus of DRSH-1/DROSHA is required for normal development and biogenesis of a subset of miRNAs.  Despite the known role of IDRs in LLPS, the role of the DRSH-1 IDR in miRNA biogenesis and development is genetically separable from its contribution to granule formation.  A cis region of an IDR-dependent miRNA confers IDR-dependence to another miRNA, suggesting that the IDR may recognize sequences or structures in the miRNA transcript. Future studies will further elucidate the specificity of this interaction and the putative role of Microprocessor condensates. Overall design: small RNA sequencing performed using NEBNext kit followed with size selection in different deletion mutants of drsh-1 in C.elegans.