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 p21WAF1/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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3' Untranslated Regions
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Alternative Splicing
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Animals
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Apoptosis
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Blotting, Northern
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Blotting, Southern
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Blotting, Western
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Cell Cycle
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Cell Cycle Proteins / metabolism*
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Cell Death
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Cell Differentiation
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Cell Survival
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Cyclin-Dependent Kinase Inhibitor p21
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Exons
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Gene Expression Regulation, Developmental
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Genetic Vectors
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Genotype
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Immunohistochemistry
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In Situ Nick-End Labeling
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Inflammation
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Lung / pathology
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Lymphocytes / metabolism
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Mice
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Mice, Transgenic
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Models, Genetic
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Molecular Sequence Data
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Muscle Cells / metabolism
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Muscle, Skeletal / metabolism
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MyoD Protein / metabolism*
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NFATC Transcription Factors
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Neurons / metabolism
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Nuclear Factor 90 Proteins
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Nuclear Proteins / metabolism
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Nuclear Proteins / physiology*
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Nucleic Acid Conformation
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Phenotype
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Protein Binding
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RNA Processing, Post-Transcriptional
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RNA, Messenger / metabolism
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Recombination, Genetic
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / metabolism
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Transcription Factors / physiology*
Substances
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3' Untranslated Regions
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Cdkn1a protein, mouse
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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DNA-Binding Proteins
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Ilf3 protein, mouse
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MyoD Protein
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NFATC Transcription Factors
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Nuclear Factor 90 Proteins
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Nuclear Proteins
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RNA, Messenger
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Transcription Factors