8FCS

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

Summary for 8FCS

• Entry DOI: 10.2210/pdb8fcs/pdb
• NMR Information: BMRB: 31061
• Descriptor: microRNA 31 (1 entity in total)
• Functional Keywords: rna, pre-mirna, dicer, dicer processing, biogenesis, pre-mir-31, mir-31, apical loop
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 22872.59

Authors

Kotar, A.,Ma, S.,Keane, S. (deposition date: 2022-12-01, release date: 2023-02-22, Last modification date: 2024-05-15)

Primary citation

Ma, S.,Kotar, A.,Grote, S.,Rouskin, S.,Keane, S.C.
Structure of pre-miR-31 reveals an active role in Dicer processing.
Biorxiv, 2023

PubMed Abstract: As an essential post-transcriptional regulator of gene expression, microRNA (miR) levels must be strictly maintained. The biogenesis of many, but not all, miRs 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 pre-miR-31 can provide a mechanism by which its biogenesis is regulated. We determined the solution structure of the precursor element of miR-31 (pre-miR-31) to investigate the role of distinct structural elements in regulating Dicer processing. We found that the presence or absence of mismatches within the helical stem do not strongly influence Dicer processing of the pre-miR. However, both the apical loop size and structure at the Dicing site are key elements for discrimination by Dicer. 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 influence both Dicer binding and processing. Our results enrich our understanding of the active role that RNA structure plays in regulating Dicer processing which has direct implications for control of gene expression.

PubMed: 36711709
DOI: 10.1101/2023.01.03.519659

Experimental method

SOLUTION NMR