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.
Grosset
C
C
Department of Biochemistry and Molecular Biology, The University of Texas Houston Medical School 77030, USA.
Chen
C Y
CY
Xu
N
N
Sonenberg
N
N
Jacquemin-Sablon
H
H
Shyu
A B
AB
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003593:Cytoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D051379:Mice; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000235:genetics; D010455:Peptides / Q000235:genetics; D011061:Poly A / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics
C079950:CSDE1 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C486686:Hnrpr protein, mouse; C000715470:MAS1 protein, human; C111580:PAIP1 protein, human; D010448:Peptide Initiation Factors; D010455:Peptides; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D011061:Poly A