Shortening of 3p UTRs in most cell types composing tumor tissues implicates alternative polyadenylation in protein metabolism

Burri, Dominik and Zavolan, Mihaela. (2021) Shortening of 3p UTRs in most cell types composing tumor tissues implicates alternative polyadenylation in protein metabolism. RNA (New York, N.Y.), 27 (12). pp. 1459-1470.

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Official URL: https://edoc.unibas.ch/84745/

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During pre-mRNA maturation 3p end processing can occur at different polyadenylation sites in the 3 prime untranslated region (3p UTR) to give rise to transcript isoforms that differ in the length of their 3p UTRs. Longer 3p UTRs contain additional cis-regulatory elements that impact the fate of the transcript and/or of the resulting protein. Extensive alternative polyadenylation (APA) has been observed in cancers, but the mechanisms and roles remain elusive. In particular, it is unclear whether the APA occurs in the malignant cells or in other cell types that infiltrate the tumor. To resolve this, we developed a computational method, called SCUREL, that quantifies changes in 3p UTR length between groups of cells, including cells of the same type originating from tumor and control tissue. We used this method to study APA in human lung adenocarcinoma (LUAD). SCUREL relies solely on annotated 3p UTRs and on control systems, such as T cell activation and spermatogenesis gives qualitatively similar results at much greater sensitivity compared to the previously published scAPA method. In the LUAD samples, we find a general trend towards 3p UTR shortening not only in cancer cells compared to the cell type of origin, but also when comparing other cell types from the tumor vs. the control tissue environment. However, we also find high variability in the individual targets between patients. The findings help to understand the extent and impact of APA in LUAD, which may support improvements in diagnosis and treatment.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela and Burri, Dominik
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Feb 2022 10:49
Deposited On:14 Feb 2022 10:47

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