| First Author | Lin K | Year | 2019 |
| Journal | Cell Rep | Volume | 26 |
| Issue | 9 | Pages | 2434-2450.e6 |
| PubMed ID | 30811992 | Mgi Jnum | J:283575 |
| Mgi Id | MGI:6381187 | Doi | 10.1016/j.celrep.2019.01.111 |
| Citation | Lin K, et al. (2019) Mammalian Pum1 and Pum2 Control Body Size via Translational Regulation of the Cell Cycle Inhibitor Cdkn1b. Cell Rep 26(9):2434-2450.e6 |
| abstractText | Body and organ size regulation in mammals involves multiple signaling pathways and remains largely enigmatic. Here, we report that Pum1 and Pum2, which encode highly conserved PUF RNA-binding proteins, regulate mouse body and organ size by post-transcriptional repression of the cell cycle inhibitor Cdkn1b. Binding of PUM1 or PUM2 to Pumilio binding elements (PBEs) in the 3' UTR of Cdkn1b inhibits translation, promoting G1-S transition and cell proliferation. Mice with null mutations in Pum1 and Pum2 exhibit gene dosage-dependent reductions in body and organ size, and deficiency for Cdkn1b partially rescues postnatal growth defects in Pum1(-/-) mice. We propose that coordinated tissue-specific expression of Pum1 and Pum2, which involves auto-regulatory and reciprocal post-transcriptional repression, contributes to the precise regulation of body and organ size. Hence PUM-mediated post-transcriptional control of cell cycle regulators represents an additional layer of control in the genetic regulation of organ and body size. |
