Emerging roles of DROSHA beyond primary microRNA processing

Abstract

DROSHA is the catalytic subunit of the Microprocessor complex, which initiates microRNA (miRNA) maturation in the nucleus by recognizing and cleaving hairpin precursors embedded in primary transcripts. However, accumulating evidence suggests that not all hairpin substrates of DROSHA are associated with the generation of functional small RNAs. By targeting those hairpins, DROSHA regulates diverse aspects of RNA metabolism across the transcriptome, serves as a line of defense against the expression of potentially deleterious elements, and permits cell fate determination and differentiation. DROSHA is also versatile in the way that it executes these noncanonical functions, occasionally depending on its RNA-binding activity rather than its catalytic activity. Herein, we discuss the functional and mechanistic diversity of DROSHA beyond the miRNA biogenesis pathway in light of recent findings.