Repeated emergence of giant microRNA hairpins across invertebrates

Javad-Zada, Mir-Mammad, Zou, Xiaodong, Okamura, Katsutomo, Shang, Renfu, Garg, Ankur, Lee, Ethan, Joshua-Tor, Leemor, Fromm, Bastian, Lai, Eric C (September 2025) Repeated emergence of giant microRNA hairpins across invertebrates. Cell Reports, 44 (9). p. 116243. ISSN 2211-1247

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URL: https://www.ncbi.nlm.nih.gov/pubmed/40934082

DOI: 10.1016/j.celrep.2025.116243

Abstract

While canonical microRNA (miRNA) hairpins typically bear 30-35 base pair (bp) stems and <15 nucleotide terminal loops, certain miRNA hairpins are much longer. While vertebrates lack long miRNA hairpins, these emerged multiple times within invertebrate lineages. Systematic assessments across >1,400 genomes provided evolutionary insights into the elongation of well-conserved miRNA precursors, which can harbor >1 kb between conserved miRNA and star species and generally form highly base-paired structures. Experiments in Drosophila and humans showed that flies were preferentially capable of maturing certain long precursors, but human cells had a partial capacity. However, neither could handle extreme miRNA hairpins. Finally, analysis of structural variants revealed that extensive stem structure and a local bulge near the dicing site are critical for biogenesis of a lengthened miRNA precursor; the latter likely represents an internal DGCR8 interaction platform. Altogether, we document unanticipated structural complexity in conserved miRNAs and emphasize bioinformatic challenges for their complete annotation.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA expression
CSHL Authors:	Garg, Ankur Joshua-Tor, Leemor
Communities:	CSHL labs > Joshua-Tor lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	9 September 2025
Date Deposited:	15 Sep 2025 12:11
Last Modified:	15 Sep 2025 12:11
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41962

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