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Site-specific release of nascent chains from ribosomes at a sense codon.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2008 Jul; Vol. 28 (13), pp. 4227-39. Date of Electronic Publication: 2008 May 05. - Publication Year :
- 2008
-
Abstract
- "2A" oligopeptides are autonomous elements containing a D(V/I)EXNPGP motif at the C terminus. Protein synthesis from an open reading frame containing an internal 2A coding sequence yields two separate polypeptides, corresponding to sequences up to and including 2A and those downstream. We show that the 2A reaction occurs in the ribosomal peptidyltransferase center. Ribosomes pause at the end of the 2A coding sequence, over the glycine and proline codons, and the nascent chain up to and including this glycine is released. Translation-terminating release factors eRF1 and eRF3 play key roles in the reaction. On the depletion of eRF1, a greater proportion of ribosomes extend through the 2A coding sequence, yielding the full-length protein. In contrast, impaired eRF3 GTPase activity leads to many ribosomes failing to translate beyond 2A. Further, high-level expression of a 2A peptide-containing protein inhibits the growth of cells compromised for release factor activity and leads to errors in stop codon recognition. We propose that the nascent 2A peptide interacts with ribosomes to drive a highly unusual and specific "termination" reaction, despite the presence of a proline codon in the A site. After this, the majority of ribosomes continue translation, generating the separate downstream product.
- Subjects :
- Amino Acid Sequence
Animals
Cattle
Codon genetics
Mice
Models, Biological
Molecular Sequence Data
Open Reading Frames
Peptide Termination Factors metabolism
Peptides chemistry
Protein Biosynthesis
RNA, Transfer, Amino Acyl metabolism
Saccharomyces cerevisiae cytology
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins metabolism
Codon metabolism
Peptides metabolism
Ribosomes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 28
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 18458056
- Full Text :
- https://doi.org/10.1128/MCB.00421-08