Nutiu, Razvan and Ma, Eric (2020) Functional atlas of primary miRNA maturation by the Microprocessor. Molecular cell. ISSN 10972765

Abstract

Primary microRNAs are the precursors of microRNAs which modulate the expression of most mRNAs in humans. They fold up into a hairpin structure that is cleaved at its base by an enzyme complex known as the Microprocessor (Drosha/DGCR8). While many of the molecular details are known, distinguishing features of primary microRNA compared to other hairpin forming transcripts be further explored. We developed a massively parallel functional assay termed Dro-seq that enabled testing of hundreds of known primary microRNA substrates and thousands of single nucleotide variants of well-known microRNAs. We found an additional feature of primary microRNAs, called Shannon entropy, describing the structural ensemble important for processing. In a deep mutagenesis experiment, we find particular apical loop U bases are likely recognized by DGCR8 and are important for efficient processing. These findings build on existing knowledge about primary miRNA maturation by Microprocessor and further explore the substrate RNA sequence-structure relationship.

Item Type:	Article
Keywords:	miRNA, miRNA biogenesis, miRNA structure, Drosha, Microprocessor
Date Deposited:	15 Dec 2020 00:45
Last Modified:	15 Dec 2020 00:45
URI:	https://oak.novartis.com/id/eprint/42692