Structure of pre-miR-31 reveals an active role in Dicer–TRBP complex processing

Ma, Sicong; Kotar, Anita; Hall, Ian; Grote, Scott; Rouskin, Silvi; Keane, Sarah C.

doi:10.1073/pnas.2300527120

Structure of pre-miR-31 reveals an active role in Dicer–TRBP complex processing

Journal Article · Tue Sep 19 00:00:00 EDT 2023 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2300527120· OSTI ID:2423658

^[1]; Kotar, Anita ^[1]; Hall, Ian ^[1]; Grote, Scott ^[2]; Rouskin, Silvi ^[2]; ^[1]

Univ. of Michigan, Ann Arbor, MI (United States)
Harvard Medical School, Boston, MA (United States)

As an essential posttranscriptional regulator of gene expression, microRNA (miRNA) levels must be strictly maintained. The biogenesis of many miRNAs is mediated by trans-acting protein partners through a variety of mechanisms, including remodeling of the RNA structure. miR-31 functions as an oncogene in numerous cancers, and interestingly, its biogenesis is not known to be regulated by protein-binding partners. Therefore, the intrinsic structural properties of the precursor element of miR-31 (pre-miR-31) can provide a mechanism by which its biogenesis is regulated. We determined the solution structure of pre-miR-31 to investigate the role of distinct structural elements in regulating processing by the Dicer–TRBP complex. We found that the presence or absence of mismatches within the helical stem does not strongly influence Dicer–TRBP processing of the pre-miRNAs. However, both the apical loop size and structure at the Dicing site are key elements for discrimination by the Dicer–TRBP complex. Interestingly, our NMR-derived structure reveals the presence of a triplet of base pairs that link the Dicer cleavage site and the apical loop. Mutational analysis in this region suggests that the stability of the junction region strongly influences processing by the Dicer–TRBP complex. Our results enrich our understanding of the active role that RNA structure plays in regulating miRNA biogenesis, which has direct implications for the control of gene expression.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2423658

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 39 Vol. 120; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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