Site-Specific Release of Nascent Chains from Ribosomes at a Sense Codon

• DOI: 10.1128/mcb.00421-08
• Publication Date: 2008-05-06T00:24:46Z
• Authors: Victoria A. Doronina; Cheng Wu; Pablo de Felipe; Matthew S. Sachs; Martin D. Ryan; Jeremy D. Brown
• Keywords: Stop codon; Release factor; Coding region; Eukaryotic Ribosome; A-site

"2A" oligopeptides are autonomous elements containing a D(V/I)EXNPGP motif at the C terminus. Protein synthesis from an open reading frame internal 2A coding sequence yields two separate polypeptides, corresponding to sequences up and including those downstream. We show that reaction occurs in ribosomal peptidyltransferase center. Ribosomes pause end of sequence, over glycine proline codons, nascent chain this is released. Translation-terminating release factors eRF1 eRF3 play key roles reaction. On depletion eRF1, greater proportion ribosomes extend through yielding full-length protein. In contrast, impaired GTPase activity leads many failing translate beyond 2A. Further, high-level expression peptide-containing protein inhibits growth cells compromised for factor errors stop codon recognition. propose peptide interacts with drive highly unusual specific "termination" reaction, despite presence A site. After this, majority continue translation, generating downstream product.