Two-motif model illuminates DICER cleavage preferences.
Nucleic Acids Res
; 52(4): 1860-1877, 2024 Feb 28.
Article
en En
| MEDLINE
| ID: mdl-38167721
ABSTRACT
In humans, DICER is a key regulator of gene expression through its production of miRNAs and siRNAs by processing miRNA precursors (pre-miRNAs), short-hairpin RNAs (shRNAs), and long double-stranded RNAs (dsRNAs). To advance our understanding of this process, we employed high-throughput dicing assays using various shRNA variants and both wild-type and mutant DICER. Our analysis revealed that DICER predominantly cleaves shRNAs at two positions, specifically at 21 (DC21) and 22 (DC22) nucleotides from their 5'-end. Our investigation identified two different motifs, mWCU and YCR, that determine whether DICER cleaves at DC21 or DC22, depending on their locations in shRNAs/pre-miRNAs. These motifs can work together or independently to determine the cleavage sites of DICER. Furthermore, our findings indicate that dsRNA-binding domain (dsRBD) of DICER enhances its cleavage, and mWCU strengthens the interaction between dsRBD and RNA, leading to an even greater enhancement of the cleavage. Conversely, YCR functions independently of dsRBD. Our study proposes a two-motif model that sheds light on the intricate regulatory mechanisms involved in gene expression by elucidating how DICER recognizes its substrates, providing valuable insights into this critical biological process.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
Tipo de estudio:
Prognostic_studies
Aspecto:
Patient_preference
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido