The sequence features that define efficient and specific hAGO2-dependent miRNA silencing guides.
Nucleic Acids Res
; 46(16): 8181-8196, 2018 09 19.
Article
em En
| MEDLINE
| ID: mdl-30239883
ABSTRACT
MicroRNAs (miRNAs) are ribonucleic acids (RNAs) of â¼21 nucleotides that interfere with the translation of messenger RNAs (mRNAs) and play significant roles in development and diseases. In bilaterian animals, the specificity of miRNA targeting is determined by sequence complementarity involving the seed. However, the role of the remaining nucleotides (non-seed) is only vaguely defined, impacting negatively on our ability to efficiently use miRNAs exogenously to control gene expression. Here, using reporter assays, we deciphered the role of the base pairs formed between the non-seed region and target mRNA. We used molecular modeling to reveal that this mechanism corresponds to the formation of base pairs mediated by ordered motions of the miRNA-induced silencing complex. Subsequently, we developed an algorithm based on this distinctive recognition to predict from sequence the levels of mRNA downregulation with high accuracy (r2 > 0.5, P-value < 10-12). Overall, our discovery improves the design of miRNA-guide sequences used to simultaneously downregulate the expression of multiple predetermined target genes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
MicroRNAs
/
Proteínas Argonautas
/
Nucleotídeos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Canadá