Browse by author
Lookup NU author(s): Dr Victoriya Doronina, Dr Jonathan Brown
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
“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.
Author(s): Doronina VA, Wu C, de Felipe P, Sachs MS, Ryan MD, Brown JD
Publication type: Article
Publication status: Published
Journal: Molecular & Cellular Biomechanics
Year: 2008
Volume: 28
Issue: 13
Pages: 4227-4239
Print publication date: 01/07/2008
ISSN (print): 1556-5297
ISSN (electronic): 1556-5300
Publisher: Tech Science Press
URL: http://dx.doi.org/10.1128/MCB.00421-08
DOI: 10.1128/MCB.00421-08
Altmetrics provided by Altmetric
