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

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 oncogen...

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Autores principales: Ma, Sicong, Kotar, Anita, Hall, Ian, Grote, Scott, Rouskin, Silvi, Keane, Sarah C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523476/
https://www.ncbi.nlm.nih.gov/pubmed/37725636
http://dx.doi.org/10.1073/pnas.2300527120
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author Ma, Sicong
Kotar, Anita
Hall, Ian
Grote, Scott
Rouskin, Silvi
Keane, Sarah C.
author_facet Ma, Sicong
Kotar, Anita
Hall, Ian
Grote, Scott
Rouskin, Silvi
Keane, Sarah C.
author_sort Ma, Sicong
collection PubMed
description 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.
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spelling pubmed-105234762023-09-28 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. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2023-09-19 2023-09-26 /pmc/articles/PMC10523476/ /pubmed/37725636 http://dx.doi.org/10.1073/pnas.2300527120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Ma, Sicong
Kotar, Anita
Hall, Ian
Grote, Scott
Rouskin, Silvi
Keane, Sarah C.
Structure of pre-miR-31 reveals an active role in Dicer–TRBP complex processing
title Structure of pre-miR-31 reveals an active role in Dicer–TRBP complex processing
title_full Structure of pre-miR-31 reveals an active role in Dicer–TRBP complex processing
title_fullStr Structure of pre-miR-31 reveals an active role in Dicer–TRBP complex processing
title_full_unstemmed Structure of pre-miR-31 reveals an active role in Dicer–TRBP complex processing
title_short Structure of pre-miR-31 reveals an active role in Dicer–TRBP complex processing
title_sort structure of pre-mir-31 reveals an active role in dicer–trbp complex processing
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523476/
https://www.ncbi.nlm.nih.gov/pubmed/37725636
http://dx.doi.org/10.1073/pnas.2300527120
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