| First Author | Mori M | Year | 2014 |
| Journal | Cell | Volume | 156 |
| Issue | 5 | Pages | 893-906 |
| PubMed ID | 24581491 | Mgi Jnum | J:211315 |
| Mgi Id | MGI:5574429 | Doi | 10.1016/j.cell.2013.12.043 |
| Citation | Mori M, et al. (2014) Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer. Cell 156(5):893-906 |
| abstractText | Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here, we show that YAP, the downstream target of the tumor-suppressive Hippo-signaling pathway regulates miRNA biogenesis in a cell-density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA-processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding posttranscriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. |
