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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gao, Qinshan Das, Biswadip Maquat, Lynne E. Sherman, Fred |
| Description | Author Affiliation: Gao Q ( Department of Biochemistry and Biophysics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 712, University of Rochester, Rochester, NY 14642, USA.); |
| Abstract | Nonsense-mediated mRNA decay (NMD) in mammalian cells is restricted to newly synthesized mRNA that is bound at the 5' cap by the major nuclear cap-binding complex and at splicing-generated exon-exon junctions by exon junction complexes. This messenger ribonucleoprotein has been called the pioneer translation initiation complex and, accordingly, NMD occurs as a consequence of nonsense codon recognition during a pioneer round of translation. Here, we characterize the nature of messenger ribonucleoprotein that is targeted for NMD in Saccharomyces cerevisiae. Data indicate that NMD targets both cap-binding complex (Cbc)1p- and eukaryotic translation initiation factor (eIF)4E-bound mRNAs, unlike in mammalian cells, where NMD does not detectably target eIF4E-bound mRNA. First, intron-containing pre-mRNAs in yeast are detectably bound by either Cbc1p, or, unlike in mammalian cells, eIF4E, indicating that mRNAs can be derived from either Cbc1p- or eIF4E-bound pre-mRNAs. Second, the ratio of nonsense-containing Cbc1p-bound mRNA to nonsense-free Cbc1p-bound mRNA, which was < 0.4 for those mRNAs tested here, is essentially identical to the ratio of the corresponding nonsense-containing eIF4E-bound mRNA to nonsense-free eIF4E-bound mRNA, and both ratios increase in cells treated with the translational inhibitor cycloheximide (CHX). These data, together with data presented here and elsewhere showing that Cbc1p-bound transcripts are precursors to eIF4E-bound transcripts, demonstrate that Cbc1p-bound mRNA is targeted for NMD. In support of the idea that eIF4E-bound mRNA is also targeted for NMD, eIF4E-bound mRNA is targeted for NMD in strains that lack Cbc1p. These results suggest that both Cbc1p- and eIF4E-mediated pioneer rounds of translation occur in yeast. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 12 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Eukaryotic Initiation Factor-4E Metabolism Protein Biosynthesis RNA Cap-Binding Proteins Saccharomyces Cerevisiae Proteins Saccharomyces Cerevisiae Genetics Cycloheximide Pharmacology DNA, Fungal Ferrochelatase Genes, Fungal Models, Biological Drug Effects RNA Precursors RNA, Fungal RNA, Messenger Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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