A mechanism for translationally coupled mRNA turnover: interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex.
mRNA turnover mediated by the major protein-coding-region determinant of instability (mCRD) of the c-fos proto-oncogene transcript illustrates a functional interplay between mRNA turnover and translation. We show that the function of mCRD depends on its distance from the poly(A) tail. Five mCRD-associated proteins were identified: Unr, a purine-rich RNA binding ... protein; PABP, a poly(A) binding protein; PAIP-1, a poly(A) binding protein interacting protein; hnRNP D, an AU-rich element binding protein; and NSAP1, an hnRNP R-like protein. These proteins form a multiprotein complex. Overexpression of these proteins stabilized mCRD-containing mRNA by impeding deadenylation. We propose that a bridging complex forms between the poly(A) tail and the mCRD and ribosome transit disrupts or reorganizes the complex, leading to rapid RNA deadenylation and decay.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Cells, Cultured, Chromosome Mapping, Cytoplasm, DNA-Binding Proteins, Gene Expression Regulation, Heterogeneous-Nuclear Ribonucleoproteins, Mice, Molecular Sequence Data, Peptide Initiation Factors, Peptides, Poly A, Protein Biosynthesis, Proto-Oncogene Proteins c-fos, RNA, Messenger, RNA-Binding Proteins, Ribonucleoproteins
Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Cells, Cultured, Chromosome Mapping, Cytoplasm, DNA-Binding Proteins, Gene Expression Regulation, Heterogeneous-Nuclear Ribonucleoproteins, Mice, Molecular Sequence Data, Peptide Initiation Factors, Peptides, Poly A, Protein Biosynthesis, Proto-Oncogene Proteins c-fos, RNA, Messenger, RNA-Binding Proteins, Ribonucleoproteins
Cell
Date: Sep. 29, 2000
PubMed ID: 11051545
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