Document Type

Article

Publication Date

7-22-2022

Publication Title

Nucleic acids research

Keywords

JGM, Animals, Humans, MicroRNAs, Ribonuclease III, Zebrafish

JAX Source

Nucleic Acids Res 2022 Jul 22; 50(13):7637-7654

Volume

50

Issue

13

First Page

7637

Last Page

7654

ISSN

1362-4962

PMID

35801921

DOI

https://doi.org/10.1093/nar/gkac568

Abstract

Although the route to generate microRNAs (miRNAs) is often depicted as a linear series of sequential and constitutive cleavages, we now appreciate multiple alternative pathways as well as diverse strategies to modulate their processing and function. Here, we identify an unusually profound regulatory role of conserved loop sequences in vertebrate pre-mir-144, which are essential for its cleavage by the Dicer RNase III enzyme in human and zebrafish models. Our data indicate that pre-mir-144 dicing is positively regulated via its terminal loop, and involves the ILF3 complex (NF90 and its partner NF45/ILF2). We provide further evidence that this regulatory switch involves reshaping of the pre-mir-144 apical loop into a structure that is appropriate for Dicer cleavage. In light of our recent findings that mir-144 promotes the nuclear biogenesis of its neighbor mir-451, these data extend the complex hierarchy of nuclear and cytoplasmic regulatory events that can control the maturation of clustered miRNAs.

Comments

This is an open-access article distributed under the terms of the Creative Commons Attribution License.

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