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Publication
Functional networks of DI3L2 in cancer
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Advisor(s)
Abstract(s)
The DIS3-like 3′-5′ exoribonuclease 2 (DIS3L2) triggers decay in an exosome-independent manner and preferentially degrades RNA species possessing a non-templated oligo-uridine 3’-end tail. It is capable of inducing decay over a variety of RNAs, including mRNAs, rRNAs, miRNAs and other non-coding RNAs. It has been shown that DIS3L2 is involved in cancer-related cellular processes. Nevertheless, its function in tumorigenesis remains largely unexplored. Recently, we and others showed that DIS3L2-mediated decay together with uridylation also participate in nonsense-mediated mRNA decay (NMD), thus revealing a new NMD branch. NMD is a surveillance pathway that recognizes and degrades mRNAs harboring premature translation-termination codons, protecting the cell from potentially harmful truncated proteins. However, NMD also regulates the level of normal and fully functional mRNAs, arising as a mechanism of gene expression regulation. Here, we aim to analyze how DIS3L2 and uridylation regulate the human transcriptome, in order to shed light on how this ribonuclease is related to NMD and how its deregulation contributes to tumorigenesis. For this purpose, high-throughput mRNA sequencing has been performed in the SW480 colorectal cancer cell line depleted of DIS3L2 or DIS3L2 plus terminal uridylyl transferases 4 and 7. Gene ontology analysis over the set of genes up-regulated under those two conditions, show enrichment in molecular functions and biological processes related with cancer, and cell events directly implicated in RNA processing and RNA degradation. Preliminary results on the features of the deregulated transcripts also show significant differences between conditions, an important aspect that is guiding us to determine grades of sensitivities in the decay of DIS3L2-subtrates. Currently, we are unveiling the role of DIS3L2 in oncogenesis and analyzing its substrate specificity.
Description
Keywords
DI3L2 Cancer mRNA Decay Doenças Genéticas Genómica Funcional e Estrutural