Essential role of the amino-terminal region of Drosha for the Microprocessor function
Summary: 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 associat...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223020485 |
| _version_ | 1797647810685829120 |
|---|---|
| author | Amit Prabhakar Song Hu Jin Tang Prajakta Ghatpande Giorgio Lagna Xuan Jiang Akiko Hata |
| author_facet | Amit Prabhakar Song Hu Jin Tang Prajakta Ghatpande Giorgio Lagna Xuan Jiang Akiko Hata |
| author_sort | Amit Prabhakar |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-11T15:21:51Z |
| format | Article |
| id | doaj.art-3e266cd1195d4f5694089fd92b89ec41 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:21:51Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3e266cd1195d4f5694089fd92b89ec412023-10-28T05:09:10ZengElsevieriScience2589-00422023-10-012610107971Essential role of the amino-terminal region of Drosha for the Microprocessor functionAmit Prabhakar0Song Hu1Jin Tang2Prajakta Ghatpande3Giorgio Lagna4Xuan Jiang5Akiko Hata6Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USAMolecular Cancer Research Center, Sun Yat-Sen University School of Medicine, Guangzhou 511400, P.R.ChinaMolecular Cancer Research Center, Sun Yat-Sen University School of Medicine, Guangzhou 511400, P.R.ChinaCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USACardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USACardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Molecular Cancer Research Center, Sun Yat-Sen University School of Medicine, Guangzhou 511400, P.R.China; Corresponding authorCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223020485Molecular biologyOmics |
| spellingShingle | Amit Prabhakar Song Hu Jin Tang Prajakta Ghatpande Giorgio Lagna Xuan Jiang Akiko Hata Essential role of the amino-terminal region of Drosha for the Microprocessor function iScience Molecular biology Omics |
| title | Essential role of the amino-terminal region of Drosha for the Microprocessor function |
| title_full | Essential role of the amino-terminal region of Drosha for the Microprocessor function |
| title_fullStr | Essential role of the amino-terminal region of Drosha for the Microprocessor function |
| title_full_unstemmed | Essential role of the amino-terminal region of Drosha for the Microprocessor function |
| title_short | Essential role of the amino-terminal region of Drosha for the Microprocessor function |
| title_sort | essential role of the amino terminal region of drosha for the microprocessor function |
| topic | Molecular biology Omics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223020485 |
| work_keys_str_mv | AT amitprabhakar essentialroleoftheaminoterminalregionofdroshaforthemicroprocessorfunction AT songhu essentialroleoftheaminoterminalregionofdroshaforthemicroprocessorfunction AT jintang essentialroleoftheaminoterminalregionofdroshaforthemicroprocessorfunction AT prajaktaghatpande essentialroleoftheaminoterminalregionofdroshaforthemicroprocessorfunction AT giorgiolagna essentialroleoftheaminoterminalregionofdroshaforthemicroprocessorfunction AT xuanjiang essentialroleoftheaminoterminalregionofdroshaforthemicroprocessorfunction AT akikohata essentialroleoftheaminoterminalregionofdroshaforthemicroprocessorfunction |