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?Alternative Polyadenylation Sites and Cancer
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By Bioinfkat, Section Biology
Posted on Fri Apr 30th, 2010 at 01:40:00 PM PST
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Alternative polyadenylation can alter the stability of the mRNA products and thus the cell's phenotype. Discovering these alternative PolyA sites and how they might alter the genetic landscape of the cell can help us understand disease phenotypes such as cancers.
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Similar to the process of alternative splicing, alternative polyadenylation can give rise to a variety of transcripts from a single gene. More than half of the human genes have multiple polyadenylation sites, leading to variable mRNA and protein products [1]. This process of alternative polyadenylation can change the length of the 3'UTR and thus the binding sites of miRNAs which tend to bind to these regions [2]. As a result, the mRNA products might become more or less stable if the sites of the polyadenylation is altered. It is possible that in a disease phenotype such as cancer, the site of the polyadenylation is changed and thus the mRNA products are not present at normal levels in the cell. The goal of this proposal is to compare the polyadenylation sites of a normal transcriptome and the cancer transcriptome of the same tissue and look for these alterations in PolyA sites. This can be accomplished by sequencing the genomes using pair-end next generation sequencing technologies. Previous studies have used single-end read RNA-seq data in fission yeast to find all the possible PolyA sites [3]. This proposal would follow the same reasoning.
1.Zhang H, et al. Genome Biol. 2005;6(12):R100.
2.Liu D, et al. Nucleic Acids Res. 2007;35(1):234-46.
3.Nagalakshmi U, et al. Science. 2008 Jun 6;320(5881):1344-9.
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