AI Article Synopsis
- Drosha is a key player in processing primary microRNAs (pri-miRNAs) and regulating about 80 ribosomal protein genes, with mutations in its amino-terminal region linked to a vascular disorder.
- Researchers created a Drosha mutant (ΔN) lacking the amino-terminal region and found it couldn't process pri-miRNAs, leading to a significant depletion of most miRNAs, except for a specific cluster (miR-183/96/182).
- The study highlights that ΔN remains stable under nutrient lack, causing increased ribosomal protein production and protein synthesis, thus allowing cells to bypass growth arrest, emphasizing the importance of Drosha-NTR in miRNA production and nutrient-responsive control of translation.
Article 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 ∼80 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558778 | PMC |
| http://dx.doi.org/10.1016/j.isci.2023.107971 | DOI Listing |
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