Inhibition of post-termination ribosome recycling at premature termination codons in UPF1 ATPase mutants
Recognition and rapid degradation of mRNA harboring premature translation termination codons (PTCs) serves to protect cells from accumulating non-functional and potentially toxic truncated polypeptides. Targeting of PTC-containing transcripts is mediated by the nonsense-mediated mRNA decay (NMD) pat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/57834 |
| _version_ | 1811236160479952896 |
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| author | Lucas D Serdar DaJuan L Whiteside Sarah L Nock David McGrath Kristian E Baker |
| author_facet | Lucas D Serdar DaJuan L Whiteside Sarah L Nock David McGrath Kristian E Baker |
| author_sort | Lucas D Serdar |
| collection | DOAJ |
| description | Recognition and rapid degradation of mRNA harboring premature translation termination codons (PTCs) serves to protect cells from accumulating non-functional and potentially toxic truncated polypeptides. Targeting of PTC-containing transcripts is mediated by the nonsense-mediated mRNA decay (NMD) pathway and requires a conserved set of proteins including UPF1, an RNA helicase whose ATPase activity is essential for NMD. Previously, we identified a functional interaction between the NMD machinery and terminating ribosomes based on 3’ RNA decay fragments that accrue in UPF1 ATPase mutants. Herein, we show that those decay intermediates originate downstream of the PTC and harbor 80S ribosomes that migrate into the mRNA 3’ UTR independent of canonical translation. Accumulation of 3’ RNA decay fragments is determined by both RNA sequence downstream of the PTC and the inactivating mutation within the active site of UPF1. Our data reveal a failure in post-termination ribosome recycling in UPF1 ATPase mutants. |
| first_indexed | 2024-04-12T12:04:10Z |
| format | Article |
| id | doaj.art-fd066d60f8264efaa942bf24035b446d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:04:10Z |
| publishDate | 2020-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fd066d60f8264efaa942bf24035b446d2022-12-22T03:33:46ZengeLife Sciences Publications LtdeLife2050-084X2020-07-01910.7554/eLife.57834Inhibition of post-termination ribosome recycling at premature termination codons in UPF1 ATPase mutantsLucas D Serdar0https://orcid.org/0000-0002-4574-1668DaJuan L Whiteside1Sarah L Nock2David McGrath3Kristian E Baker4https://orcid.org/0000-0003-2262-5434Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, United States; Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, United StatesDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, United StatesDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, United StatesDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, United StatesDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, United States; Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, United StatesRecognition and rapid degradation of mRNA harboring premature translation termination codons (PTCs) serves to protect cells from accumulating non-functional and potentially toxic truncated polypeptides. Targeting of PTC-containing transcripts is mediated by the nonsense-mediated mRNA decay (NMD) pathway and requires a conserved set of proteins including UPF1, an RNA helicase whose ATPase activity is essential for NMD. Previously, we identified a functional interaction between the NMD machinery and terminating ribosomes based on 3’ RNA decay fragments that accrue in UPF1 ATPase mutants. Herein, we show that those decay intermediates originate downstream of the PTC and harbor 80S ribosomes that migrate into the mRNA 3’ UTR independent of canonical translation. Accumulation of 3’ RNA decay fragments is determined by both RNA sequence downstream of the PTC and the inactivating mutation within the active site of UPF1. Our data reveal a failure in post-termination ribosome recycling in UPF1 ATPase mutants.https://elifesciences.org/articles/57834nonsense mediated decayUPF1translationribosome recyclingtermination |
| spellingShingle | Lucas D Serdar DaJuan L Whiteside Sarah L Nock David McGrath Kristian E Baker Inhibition of post-termination ribosome recycling at premature termination codons in UPF1 ATPase mutants eLife nonsense mediated decay UPF1 translation ribosome recycling termination |
| title | Inhibition of post-termination ribosome recycling at premature termination codons in UPF1 ATPase mutants |
| title_full | Inhibition of post-termination ribosome recycling at premature termination codons in UPF1 ATPase mutants |
| title_fullStr | Inhibition of post-termination ribosome recycling at premature termination codons in UPF1 ATPase mutants |
| title_full_unstemmed | Inhibition of post-termination ribosome recycling at premature termination codons in UPF1 ATPase mutants |
| title_short | Inhibition of post-termination ribosome recycling at premature termination codons in UPF1 ATPase mutants |
| title_sort | inhibition of post termination ribosome recycling at premature termination codons in upf1 atpase mutants |
| topic | nonsense mediated decay UPF1 translation ribosome recycling termination |
| url | https://elifesciences.org/articles/57834 |
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