Essential role of the amino-terminal region of Drosha for the Microprocessor function.
iScience
; 26(10): 107971, 2023 Oct 20.
Article
em En
| MEDLINE
| ID: mdl-37810246
ABSTRACT
Drosha is a core component of the Microprocessor complex that cleaves primary-microRNAs (pri-miRNAs) to generate precursor-miRNA and regulates the expression of â¼80 ribosomal protein (RP) genes. Despite the fact that mutations in the amino-terminal region of Drosha (Drosha-NTR) are associated with a vascular disorder, hereditary hemorrhagic telangiectasia, the precise function of Drosha-NTR remains unclear. By deleting exon 5 from the Drosha gene and generating a Drosha mutant lacking the NTR (ΔN), we demonstrate that ΔN is unable to process pri-miRNAs, which leads to a global miRNA depletion, except for the miR-183/96/182 cluster. We find that Argonaute 2 facilitates the processing of the pri-miR-183/96/182 in ΔN cells. Unlike full-length Drosha, ΔN is not degraded under serum starvation, resulting in unregulated RP biogenesis and protein synthesis in ΔN cells, allowing them to evade growth arrest. This study reveals the essential role of Drosha-NTR in miRNA production and nutrient-dependent translational control.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article