Repeated emergence of giant microRNA hairpins across invertebrates Journal Article


Authors: Javad-zada, M. M.; Zou, X. D.; Okamura, K.; Shang, R. F.; Garg, A.; Lee, E.; Joshua-Tor, L.; Fromm, B.; Lai, E. C.
Article Title: Repeated emergence of giant microRNA hairpins across invertebrates
Abstract: <p>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.</p>
Keywords: evolution; recognition; posttranscriptional regulation; biogenesis; small rnas; expression; pathway; precursors; utr sequence motif; uniform system
Journal Title: Cell Reports
Volume: 44
Issue: 9
ISSN: 2639-1856
Publisher: Cell Press  
Date Published: 2025-09-23
Start Page: 116243
Language: English
ACCESSION: WOS:001572401200001
DOI: 10.1016/j.celrep.2025.116243
PROVIDER: wos
PUBMED: 40934082
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Eric C. Lai -- Source: Wos
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MSK Authors
  1. Eric C Lai
    160 Lai
  2. Katsutomo Okamura
    27 Okamura