{"oa_version":"Published Version","language":[{"iso":"eng"}],"external_id":{"pmid":["38289956"]},"type":"journal_article","article_type":"original","issue":"6","publication":"Proceedings of the National Academy of Sciences","date_updated":"2025-01-29T08:44:35Z","_id":"18938","author":[{"full_name":"Springstein, Benjamin L","last_name":"Springstein","orcid":"0000-0002-3461-5391","id":"b4eb62ef-ac72-11ed-9503-ed3b4d66c083","first_name":"Benjamin L"},{"full_name":"Paulo, Joao A.","last_name":"Paulo","first_name":"Joao A."},{"first_name":"Hankum","full_name":"Park, Hankum","last_name":"Park"},{"first_name":"Kemardo","full_name":"Henry, Kemardo","last_name":"Henry"},{"first_name":"Eleanor","last_name":"Fleming","full_name":"Fleming, Eleanor"},{"first_name":"Zoë","full_name":"Feder, Zoë","last_name":"Feder"},{"first_name":"J. Wade","full_name":"Harper, J. Wade","last_name":"Harper"},{"first_name":"Ann","full_name":"Hochschild, Ann","last_name":"Hochschild"}],"OA_type":"hybrid","day":"06","quality_controlled":"1","OA_place":"publisher","department":[{"_id":"MaLo"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","volume":121,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"date_published":"2024-02-06T00:00:00Z","has_accepted_license":"1","abstract":[{"text":"The synthesis of proteins as encoded in the genome depends critically on translational fidelity. Nevertheless, errors inevitably occur, and those that result in reading frame shifts are particularly consequential because the resulting polypeptides are typically nonfunctional. Despite the generally maladaptive impact of such errors, the proper decoding of certain mRNAs, including many viral mRNAs, depends on a process known as programmed ribosomal frameshifting. The fact that these programmed events, commonly involving a shift to the –1 frame, occur at specific evolutionarily optimized “slippery” sites has facilitated mechanistic investigation. By contrast, less is known about the scope and nature of error (i.e., nonprogrammed) frameshifting. Here, we examine error frameshifting by monitoring spontaneous frameshift events that suppress the effects of single base pair deletions affecting two unrelated test proteins. To map the precise sites of frameshifting, we developed a targeted mass spectrometry–based method called “translational tiling proteomics” for interrogating the full set of possible –1 slippage events that could produce the observed frameshift suppression. Surprisingly, such events occur at many sites along the transcripts, involving up to one half of the available codons. Only a subset of these resembled canonical “slippery” sites, implicating alternative mechanisms potentially involving noncognate mispairing events. Additionally, the aggregate frequency of these events (ranging from 1 to 10% in our test cases) was higher than we might have anticipated. Our findings point to an unexpected degree of mechanistic diversity among ribosomal frameshifting events and suggest that frameshifted products may contribute more significantly to the proteome than generally assumed.","lang":"eng"}],"publication_status":"published","title":"Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics","oa":1,"file":[{"relation":"main_file","date_updated":"2025-01-29T08:43:16Z","content_type":"application/pdf","access_level":"open_access","date_created":"2025-01-29T08:43:16Z","success":1,"creator":"dernst","file_name":"2024_PNAS_Springstein.pdf","file_size":720902,"file_id":"18939","checksum":"5bd62c7cb4287e3706a1d45d6ef61fd1"}],"intvolume":"       121","month":"02","year":"2024","scopus_import":"1","pmid":1,"article_number":"e2317453121","file_date_updated":"2025-01-29T08:43:16Z","acknowledgement":"We thank S. L. Dove for valuable discussion and comments on the manuscript and R. Hellmiss for artwork. This work was supported by NIH grants GM136247 to A.H., AG011085 to J.W.H., and GM132129 to J.A.P.","date_created":"2025-01-29T08:39:27Z","publisher":"National Academy of Sciences","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"citation":{"ista":"Springstein BL, Paulo JA, Park H, Henry K, Fleming E, Feder Z, Harper JW, Hochschild A. 2024. Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics. Proceedings of the National Academy of Sciences. 121(6), e2317453121.","mla":"Springstein, Benjamin L., et al. “Systematic Analysis of Nonprogrammed Frameshift Suppression in E.Coli via Translational Tiling Proteomics.” <i>Proceedings of the National Academy of Sciences</i>, vol. 121, no. 6, e2317453121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2317453121\">10.1073/pnas.2317453121</a>.","short":"B.L. Springstein, J.A. Paulo, H. Park, K. Henry, E. Fleming, Z. Feder, J.W. Harper, A. Hochschild, Proceedings of the National Academy of Sciences 121 (2024).","ama":"Springstein BL, Paulo JA, Park H, et al. Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics. <i>Proceedings of the National Academy of Sciences</i>. 2024;121(6). doi:<a href=\"https://doi.org/10.1073/pnas.2317453121\">10.1073/pnas.2317453121</a>","apa":"Springstein, B. L., Paulo, J. A., Park, H., Henry, K., Fleming, E., Feder, Z., … Hochschild, A. (2024). Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2317453121\">https://doi.org/10.1073/pnas.2317453121</a>","chicago":"Springstein, Benjamin L, Joao A. Paulo, Hankum Park, Kemardo Henry, Eleanor Fleming, Zoë Feder, J. Wade Harper, and Ann Hochschild. “Systematic Analysis of Nonprogrammed Frameshift Suppression in E.Coli via Translational Tiling Proteomics.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2317453121\">https://doi.org/10.1073/pnas.2317453121</a>.","ieee":"B. L. Springstein <i>et al.</i>, “Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics,” <i>Proceedings of the National Academy of Sciences</i>, vol. 121, no. 6. National Academy of Sciences, 2024."},"status":"public","doi":"10.1073/pnas.2317453121","article_processing_charge":"No","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"}