Malka, Yuval Alkan, Ferhat 주신영 K？rner, Pierre-Rene Pataskar, Abhijeet Shulman, Eldad Loayza-Puch, Fabricio Champagne, Julien Wenzel, Casper Faller, William James Elkon, Ran Lee, Cheolju Agami, Reuven 2024-01-12T02:36:23Z 2024-01-12T02:36:23Z 2022-11-09 2022-10 1097-2765 https://pubs.kist.re.kr/handle/201004/75980 The use of alternative promoters, splicing, and cleavage and polyadenylation (APA) generates mRNA iso-forms that expand the diversity and complexity of the transcriptome. Here, we uncovered thousands of pre-viously 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 pro-motes 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. English Cell Press Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential Article 10.1016/j.molcel.2022.09.036 1 Molecular Cell, v.82, no.20, pp.3840 - 3855.e8 Molecular Cell 82 20 3840 3855.e8 N scie scopus 000880784300012 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article CELLS REVEALS METHYLATION EXPRESSION TRANSCRIPTION STRESS MAP N-6-METHYLADENOSINE DEGRADATION COMPLEXITY EFFICIENCY