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Jones, A. ; Walbrun, A.* ; Falleroni, F.* ; Rief, M.* ; Sattler, M.

Conformational effects of a cancer-linked mutation in pri-miR-30c RNA.

J. Mol. Biol. 434:167705 (2022)
Postprint DOI PMC
Open Access Green
MicroRNAs (miRNAs) are small, noncoding RNAs that mediate post-transcriptional downregulation of specific target genes. These transcripts are the products of a two-step processing pathway; primary miRNAs (pri-miRNAs) are processed by Drosha into individual precursor miRNA (pre-miRNA) hairpins, which are subsequently processed by Dicer into mature miRNAs. Single nucleotide polymorphisms (SNPs) that occur in pri-miRNAs, pre-miRNAs and mature miRNAs have been shown to affect the processing of specific target genes by modulating Drosha and Dicer processing or interactions with RNA binding proteins (RBPs). Using NMR and single-molecule optical tweezer experiments, we have investigated the conformational effects of a cancer-linked G/A mutation in the terminal loop of pri-miR-30c RNA, and how this influences binding by the SRSF3 and hnRNP A1 RBPs, which are implicated in its processing. Our results reveal that the wildtype and G/A variant pri-miR-30c RNAs adopt very similar elongated stem-loop structures, both of which are bound by SRSF3. However, while both wildtype and G/A pri-miR-30c RNAs can form dimeric kissing hairpin structures, the G to A mutation results in partial destabilization of the dimer in the variant transcript. This promotes recognition and binding by hnRNP A1, an RBP that enhances pri-miR-30c processing. Our data provide structural insight into the conformational effects of a G/A mutation in pri-miR-30c RNA and how this could affect processing and promote cancer.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Nmr ; Saxs ; Snp ; Srsf3 ; Hnrnp A1 ; Kissing Hairpin ; Optical Tweezers ; Pri-mirna
ISSN (print) / ISBN 0022-2836
e-ISSN 1089-8638
Journal Journal of Molecular Biology
Quellenangaben Volume: 434, Issue: 18, Pages: , Article Number: 167705 Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
Grants Horizon 2020
Deutsche Forschungsgemeinschaft
European Research Council
Horizon 2020 Framework Programme
Frank Gabel