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Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential
The use of alternative promoters, splicing, and cleavage and polyadenylation (APA) generates mRNA isoforms that expand the diversity and complexity of the transcriptome. Here, we uncovered thousands of previously undescribed 5′ uncapped and polyadenylated transcripts (5′ UPTs). We show that these tr...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636002/ https://www.ncbi.nlm.nih.gov/pubmed/36270248 http://dx.doi.org/10.1016/j.molcel.2022.09.036 |
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author | Malka, Yuval Alkan, Ferhat Ju, Shinyeong Körner, Pierre-Rene Pataskar, Abhijeet Shulman, Eldad Loayza-Puch, Fabricio Champagne, Julien Wenzel, Casper Faller, William James Elkon, Ran Lee, Cheolju Agami, Reuven |
author_facet | Malka, Yuval Alkan, Ferhat Ju, Shinyeong Körner, Pierre-Rene Pataskar, Abhijeet Shulman, Eldad Loayza-Puch, Fabricio Champagne, Julien Wenzel, Casper Faller, William James Elkon, Ran Lee, Cheolju Agami, Reuven |
author_sort | Malka, Yuval |
collection | PubMed |
description | The use of alternative promoters, splicing, and cleavage and polyadenylation (APA) generates mRNA isoforms that expand the diversity and complexity of the transcriptome. Here, we uncovered thousands of previously undescribed 5′ uncapped and polyadenylated transcripts (5′ UPTs). We show that these transcripts resist exonucleases due to a highly structured RNA and N6-methyladenosine modification at their 5′ termini. 5′ UPTs appear downstream of APA sites within their host genes and are induced upon APA activation. Strong enrichment in polysomal RNA fractions indicates 5′ UPT translational potential. Indeed, APA promotes downstream translation initiation, non-canonical protein output, and consistent changes to peptide presentation at the cell surface. Lastly, we demonstrate the biological importance of 5′ UPTs using Bcl2, a prominent anti-apoptotic gene whose entire coding sequence is a 5′ UPT generated from 5′ UTR-embedded APA sites. Thus, APA is not only accountable for terminating transcripts, but also for generating downstream uncapped RNAs with translation potential and biological impact. |
format | Online Article Text |
id | pubmed-9636002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-96360022022-11-07 Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential Malka, Yuval Alkan, Ferhat Ju, Shinyeong Körner, Pierre-Rene Pataskar, Abhijeet Shulman, Eldad Loayza-Puch, Fabricio Champagne, Julien Wenzel, Casper Faller, William James Elkon, Ran Lee, Cheolju Agami, Reuven Mol Cell Article The use of alternative promoters, splicing, and cleavage and polyadenylation (APA) generates mRNA isoforms that expand the diversity and complexity of the transcriptome. Here, we uncovered thousands of previously undescribed 5′ uncapped and polyadenylated transcripts (5′ UPTs). We show that these transcripts resist exonucleases due to a highly structured RNA and N6-methyladenosine modification at their 5′ termini. 5′ UPTs appear downstream of APA sites within their host genes and are induced upon APA activation. Strong enrichment in polysomal RNA fractions indicates 5′ UPT translational potential. Indeed, APA promotes downstream translation initiation, non-canonical protein output, and consistent changes to peptide presentation at the cell surface. Lastly, we demonstrate the biological importance of 5′ UPTs using Bcl2, a prominent anti-apoptotic gene whose entire coding sequence is a 5′ UPT generated from 5′ UTR-embedded APA sites. Thus, APA is not only accountable for terminating transcripts, but also for generating downstream uncapped RNAs with translation potential and biological impact. Cell Press 2022-10-20 /pmc/articles/PMC9636002/ /pubmed/36270248 http://dx.doi.org/10.1016/j.molcel.2022.09.036 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Malka, Yuval Alkan, Ferhat Ju, Shinyeong Körner, Pierre-Rene Pataskar, Abhijeet Shulman, Eldad Loayza-Puch, Fabricio Champagne, Julien Wenzel, Casper Faller, William James Elkon, Ran Lee, Cheolju Agami, Reuven Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential |
title | Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential |
title_full | Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential |
title_fullStr | Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential |
title_full_unstemmed | Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential |
title_short | Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential |
title_sort | alternative cleavage and polyadenylation generates downstream uncapped rna isoforms with translation potential |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636002/ https://www.ncbi.nlm.nih.gov/pubmed/36270248 http://dx.doi.org/10.1016/j.molcel.2022.09.036 |
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