E-MTAB-6403
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-6403 | ExpressionAtlas | 2025-01-23
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-MTAB-6403-analysis-methods.tsv | Tabular | |||
| E-MTAB-6403-analytics.tsv | Tabular | |||
| E-MTAB-6403-atlasExperimentSummary.Rdata | Rdata | |||
| E-MTAB-6403-configuration.xml | Xml | |||
| E-MTAB-6403-g2_g1-mvaPlot.png | Other |
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Project description:The tumorigenesis of small intestinal neuroendocrine tumors (NETs) is poorly understood. Recent studies have associated alternative polyadenylation with proliferation, cell transformation and cancer. Polyadenylation is the process in which the pre-mRNA is cleaved at a polyA site and a polyA tail is added. Genes with two or more polyA sites can undergo alternative polyadenylation. This produces two or more distinct mRNA isoforms with different 3M-bM-^@M-^Y untranslated regions. Additionally, alternative polyadenylation can also produce mRNAs containing different 3M-bM-^@M-^Y-terminal coding regions. Therefore, alternative polyadenylation alters both the repertoire and the expression level of proteins. Here we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three small intestinal neuroendocrine tumors and a reference sample. In the tumors sixteen genes showed significant changes of alternative polyadenylation pattern, which lead to either the 3M-bM-^@M-^Y truncation of mRNA coding regions or 3M-bM-^@M-^Y untranslated regions. Among these, 11 genes had been previously associated with cancer, with 4 genes being known tumor suppressors: DCC, PDZD2, MAGI1 and DACT2. We validated the alternative polyadenylation in 3 out of 3 cases with Q-RT-PCR. Our findings suggest that changes of alternative polyadenylation pattern in these 16 genes could be involved in the tumorigenesis of small intestinal neuroendocrine tumors. Furthermore, they also point to alternative polyadenylation as a new target for both diagnostic and treatment of small intestinal neuroendocrine tumors. The identified genes with alternative polyadenylation specific to the small intestinal neuroendocrine tumors could be further tested as diagnostic markers and drug targets for disease prevention and treatment. PolyA-seq profiling of 3 human neuroendocrine tumors compared and pituitary using Direct RNA Sequencing from Helicos Biosciences Technology
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Project description:The use of alternative polyadenylation sites is common and affects the post-transcriptional fate of mRNA, including its stability, localization, and translation. Here we present a method for genome-wide and strand-specific mapping of poly(A) sites and quantification of RNA levels at unprecedented efficiency by using an on-cluster dark T-fill procedure on the Illumina sequencing platform. Our method outperforms former protocols in quality and throughput, and reveals new insights into polyadenylation in Saccharomyces cerevisiae. Experimental benchmark of five different protocols (3tfill, bpmI, internal, rnaseq and yoon) for genome-wide identification of polyadenylation sites in Saccharomyces cerevisiae and transcript quantification. RNA was extracted from WT cells grown in glucose (ypd) or galactose (ypgal) as carbon source. The same RNA was used for 3 independent library constructions (technical replicates, rep).
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