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. 2023 Jan 13;12(2):306. doi: 10.3390/cells12020306

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© 2023 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Structural basis of efficient pri-miRNA processing. (a) Outline of the canonical miRNA biogenesis. (b) The structure of pri-miRNA and related molecules are demonstrated. The numbers in parentheses indicate the features of the miRNA precursor sequences contributing to efficient pri-miRNA processing. (1) UG and UGU motifs are recognized by DROSHA and DGCR8, respectively. Thus, the DROSHA–DGCR8 complex contributes to the correct measurement of the miRNA basal stem length. (2) A CNNF motif is bound by SRSF3. SRSF3s have multifaceted roles in miRNA processing by facilitating pri-miRNA processing efficiency, modulating alternative processing, and preventing 5p-nick processing and inverse processing. (3) An mGHG motif is bound by the dsRBD of DROSHA and helps DROSHA identify the miRNA cleavage site. (4) The large-sized asymmetric internal loops, i.e., large-sized mismatches, inhibit the cleavage of the 3p strand and therefore downregulate miRNA expression. Pri-miRNA, primary miRNA; mGHG, mismatched GHG; dsRBD, double-stranded RNA binding domain.