{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:39:56Z","timestamp":1788431996862,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/I020926\/1,BB\/N017161\/1"],"award-info":[{"award-number":["BB\/I020926\/1,BB\/N017161\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In eukaryotes, the binding of poly(A) binding protein (PAB) to the poly(A) tail is central to maintaining mRNA stability. PABP interacts with the translation termination apparatus, and with eIF4G to maintain 3\u2032\u20135\u2032 mRNA interactions as part of an mRNA closed loop. It is however unclear how ribosome recycling on a closed loop mRNA is influenced by the proximity of the stop codon to the poly(A) tail, and how post-termination ribosome recycling affects mRNA stability. We show that in a yeast disabled for nonsense mediated mRNA decay (NMD), a PGK1 mRNA with an early stop codon at codon 22 of the reading frame is still highly unstable, and that this instability cannot be significantly countered even when 50% stop codon readthrough is triggered. In an NMD-deficient mutant yeast, stable reporter alleles with more 3\u2032 proximal stop codons could not be rendered unstable through Rli1-depletion, inferring defective Rli1 ribosome recycling is insufficient in itself to trigger mRNA instability. Mathematical modelling of a translation system including the effect of ribosome recycling and poly(A) tail shortening supports the hypothesis that impaired ribosome recycling from 5\u2032 proximal stop codons may compromise initiation processes and thus destabilize the mRNA. A model is proposed wherein ribosomes undergo a maturation process during early elongation steps, and acquire competency to re-initiate on the same mRNA as translation elongation progresses beyond the very 5\u2032 proximal regions of the mRNA.<\/jats:p>","DOI":"10.3390\/cells8080800","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T11:37:07Z","timestamp":1564573027000},"page":"800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Destabilization of Eukaryote mRNAs by 5\u2032 Proximal Stop Codons Can Occur Independently of the Nonsense-Mediated mRNA Decay Pathway"],"prefix":"10.3390","volume":"8","author":[{"given":"Barbara","family":"Gorgoni","sequence":"first","affiliation":[{"name":"Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3684-5297","authenticated-orcid":false,"given":"Yun-Bo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Centre for Process Systems Engineering, Institute for Systems and Synthetic Biology, Imperial College London, South Kensington Campus, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Centre for Process Systems Engineering, Institute for Systems and Synthetic Biology, Imperial College London, South Kensington Campus, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-7906","authenticated-orcid":false,"given":"Ian","family":"Stansfield","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1534\/genetics.111.137265","article-title":"RNA degradation in Saccharomyces cerevisiae","volume":"191","author":"Parker","year":"2012","journal-title":"Genetics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nrm2104","article-title":"The highways and byways of mRNA decay","volume":"8","author":"Garneau","year":"2007","journal-title":"Nat. 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