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| Content Provider | PubMed Central |
|---|---|
| Author | Yang, Qian Li, Wenming She, Hua Dou, Juan Duong, Duc M. Du, Yuhong Yang, Shao-hua Seyfried, Nicholas T. Fu, Haian Gao, Guodong Mao, Zixu |
| Copyright Year | 2015 |
| Abstract | MicroRNAs (miRNAs) regulate the translational potential of their mRNA targets and control many cellular processes. The key step in canonical miRNA biogenesis is the cleavage of the primary transcripts by the nuclear RNase III enzyme Drosha. Emerging evidence suggests that the miRNA biogenic cascade is tightly controlled. However, little is known whether Drosha is regulated. Here we show that Drosha is targeted by stress. Under stress, p38 MAPK directly phosphorylates Drosha at its N-terminus. This reduces its interaction with DiGeorge syndrome critical region 8, and promotes its nuclear export and degradation by calpain. This regulatory mechanism mediates stress-induced inhibition of Drosha function. Reduction of Drosha sensitizes cells to stress and increases death. In contrast, increase in Drosha attenuates stress-induced death. These findings reveal a critical regulatory mechanism by which stress engages p38 MAPK pathway to destabilize Drosha and inhibit Drosha-mediated cellular survival. |
| Related Links | http://dx.doi.org/10.1016/j.molcel.2015.01.004 |
| Ending Page | 734 |
| Page Count | 14 |
| Starting Page | 721 |
| File Format | |
| ISSN | 10972765 |
| e-ISSN | 10974164 |
| Journal | Molecular cell |
| Issue Number | 4 |
| Volume Number | 57 |
| Language | English |
| Publisher Date | 2015-02-01 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology |
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