Genetic variation and RNA structure regulate microRNA biogenesis.
Nat Commun
; 8: 15114, 2017 05 03.
Article
em En
| MEDLINE
| ID: mdl-28466845
ABSTRACT
MiRNA biogenesis is highly regulated at the post-transcriptional level; however, the role of sequence and secondary RNA structure in this process has not been extensively studied. A single G to A substitution present in the terminal loop of pri-mir-30c-1 in breast and gastric cancer patients had been previously described to result in increased levels of mature miRNA. Here, we report that this genetic variant directly affects Drosha-mediated processing of pri-mir-30c-1 in vitro and in cultured cells. Structural analysis of this variant revealed an altered RNA structure that facilitates the interaction with SRSF3, an SR protein family member that promotes pri-miRNA processing. Our results are compatible with a model whereby a genetic variant in pri-mir-30c-1 leads to a secondary RNA structure rearrangement that facilitates binding of SRSF3 resulting in increased levels of miR-30c. These data highlight that primary sequence determinants and RNA structure are key regulators of miRNA biogenesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Processamento Pós-Transcricional do RNA
/
MicroRNAs
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article