{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:10:27Z","timestamp":1788862227935,"version":"build-2803163510"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP1GM142101"],"award-info":[{"award-number":["DP1GM142101"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Viral 2A oligopeptides drive an unusual ribosome recoding event in which peptide-bond formation fails at a conserved PG\u2193P motif, producing two discrete proteins without canonical termination. Despite decades of study, the molecular basis of 2A-mediated peptide-bond skipping remains poorly understood. Here, we combine quantitative 2A reporters with high-resolution ribosome profiling to interrogate ribosome dynamics at the core 2A sequences. We identify a pausing event at the terminal proline codon of the PGP motif that functions as a kinetic decision point: ribosome dwell time at this site inversely correlates with skipping efficiency. Increasing nascent chain flexibility by inserting linkers immediately upstream of the 2A sequence reduces ribosome occupancy at the terminal proline codon and enhances peptide-bond skipping. Strikingly, amino acid repeats positioned distally upstream also modulate 2A activity, indicating long-range coupling between nascent chain properties outside of the ribosome and the peptidyl transferase center inside the ribosome. In particular, hydrophobic residues potently suppress skipping, an effect that can be rescued by extending flexible segments within the peptide exit tunnel. Together, our findings support a model in which nascent chain features\u2014beyond the core 2A motif\u2014dynamically tune ribosomal recoding efficiency through co-translational feedback into the catalytic center.<\/jats:p>","DOI":"10.1093\/nar\/gkag875","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:34:09Z","timestamp":1788521649000},"source":"Crossref","is-referenced-by-count":0,"title":["Ribosome dynamics at the conserved PGP motif governs 2A peptide-bond-skipping efficiency"],"prefix":"10.1093","volume":"54","author":[{"given":"Xincheng","family":"Wu","sequence":"first","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University , Ithaca, NY 14853 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University , Ithaca, NY 14853 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University , Ithaca, NY 14853 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4127-1136","authenticated-orcid":false,"given":"Shu-Bing","family":"Qian","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University , Ithaca, NY 14853 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"2026090805163886300_B1","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.1099\/0022-1317-72-11-2727","article-title":"Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid 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