1. NF90 Regulates Cell Cycle Exit and Terminal Myogenic Differentiation by Direct Binding to the 3′-Untranslated Region of MyoD and p21WAF1/CIP1 mRNAs.
- Author
-
Lingfang Shi, Guohua Zhao, Daoming Qiu, Godfrey, Wayne R., Vogel, Hannes, Rando, Thomas A., Hong Hu, and Kao, Peter N.
- Subjects
- *
GENE expression , *CELL cycle regulation , *RNA-protein interactions , *PROTEIN binding , *MYOBLASTS , *CELLULAR control mechanisms , *GENETIC transcription , *MESSENGER RNA - Abstract
NF90 and splice variant NF110/ILF3/NFAR are double-stranded RNA-binding proteins that regulate gene expression. Mice with targeted disruption of NF90 were engineered. NF90(-/-) mice were born small and weak and succumbed to perinatal death within 12 h because of neuromuscular respiratory failure. Lung inflation and morphology were normal in NF90(-/-) mice. The diaphragm and other skeletal muscles in NF90(-/-) mice demonstrated disorganized arrangement and paucity of myofibers, evidence of myocyte degeneration and increased apoptosis. The expression of myogenic regulators, MyoD, myogenin, and p21WAF1/CIP1, was severely decreased in NF90(-/-) mice. These myogenic transcription factors and cell cycle inhibitors are regulated in part through post-transcriptional mRNA stabilization. Northwestern blotting revealed that NF90 is the principal and specific p21 WAF1/CIP1 and MyoD 3′-untranslated region RNA-binding protein in developing skeletal muscles. NF90 regulates transcription factors and a cell cycle inhibitor essential for skeletal muscle differentiation and for survival. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF