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Genome-wide profiling reveals cancer-related genes have switched alternative polyadenylation sites in colorectal cancer

ABSTRACT: Genome-wide profiling reveals cancer-related genes have switched alternative polyadenylation sites in colorectal cancer

PROVIDER: PRJEB24581 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR2263460_1.fastq.gz	Fastqsanger.gz
	ERR2263460_2.fastq.gz	Fastqsanger.gz
	ERR2263455_1.fastq.gz	Fastqsanger.gz
	ERR2263455_2.fastq.gz	Fastqsanger.gz
	ERR2263456_1.fastq.gz	Fastqsanger.gz

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Genome-wide profiling reveals cancer-related genes have switched alternative polyadenylation sites in colorectal cancer

Project description:Alternative polyadenylation (APA) is a kind of important post-transcriptional modification in eukaryotic cells. It plays considerable roles in many biological processes and diseases, such as cell differentiation, proliferation and cancer. Here, we used a high-throughput sequencing-based method 3T-seq to investigate the APA pattern in three colorectal cancer patients and explored the biological significance of APA modulation in all the three patients.

2018-02-02 | E-MTAB-6403 | biostudies-arrayexpress

Genome-wide profiling reveals cancer-related genes with switched alternative polyadenylation sites in colorectal cancer.

Project description:BackgroundAlternative polyadenylation (APA) is an important post-transcriptional regulation in eukaryotic cells. It plays considerable roles in many biological processes and diseases, such as cell differentiation, proliferation and cancer. Colorectal cancer (CRC) is one of the most common malignancies worldwide, which is among the top five in incidence and mortality of all cancers in China. Although there have been some studies on the APA of CRC, the normal and carcinoma samples used for genome-wide profiling were not matched. The purpose of this study was to obtain genes with switched 3'-untranslated region (UTR) that may be associated with intracellular regulation of CRC by analyzing APA patterns of strict control groups from clinical patients.Materials and methodsCRC and matched normal tissues were acquired from surgical specimens from three CRC patients. Their libraries of 3'-terminal fragments of mRNA with poly(A) tails were constructed by 3T-seq technology and sequenced by Illumina Hiseq X Ten. APA patterns of cancer and matched normal tissues were analyzed by bioinformatics analysis, and a representative gene, GPI, was verified by quantitative reverse transcription PCR.ResultsOverall, we identified 35,076 poly(A) sites in total. Compared to the matched normal tissues, we detected 350, 405 and 375 genes with significantly APA-mediated 3'-UTR alteration in cancer tissues of three patients, respectively. Forty-seven genes with switched 3'-UTR were shared in all three patients. In addition, most of these genes have shortened 3'-UTRs, some of which were associated with cancers, such as GPI.ConclusionOur studies found several genes with switched 3'-UTR in CRC patients, which may provide some important clues for more in-depth study of the cellular regulation in CRC from the perspective of post-transcriptional regulation. It may also help in the search for new biomarkers of CRC.

| S-EPMC6126484 | biostudies-literature

Mouse alternative polyadenylation

Project description:Divergence of alternative polyadenylation in mouse

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Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns

Project description:Alternative polyadenylation has been implicated as an important regulator of gene expression. In some cases, alternative polyadenylation is known to couple with alternative splicing to influence last intron removal. However, it is unknown whether alternative polyadenylation events influence alternative splicing decisions at upstream exons. Knockdown of the polyadenylation factors CFIm25 or CstF64 was used as an approach in identifying alternative polyadenylation and alternative splicing events on a genome-wide scale. Although hundreds of alternative splicing events were found to be differentially spliced in the knockdown of CstF64, genes associated with alternative polyadenylation did not exhibit an increased incidence of alternative splicing. These results demonstrate that the coupling between alternative polyadenylation and alternative splicing is usually limited to defining the last exon. The striking influence of CstF64 knockdown on alternative splicing can be explained through its effects on UTR selection of known splicing regulators such as hnRNP A2/B1, thereby indirectly influencing splice site selection. We conclude that changes in the expression of the polyadenylation factor CstF64 influences alternative splicing through indirect effects. HeLa cell line was stably transfected with shRNA plasmids targeting CstF64. Total RNA was isolated from CstF64 KD cells and wild-type control cells using Trizol according to manufacturerâs protocols. Samples were deep sequenced in duplicate using the Illumina GAIIx system.

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AMPKα1 and α2 knockout and usage of alternative polyadenylation sites

Project description:Role of alternative polyadenylation in muscle development remains largely undetermined. Our WTTS-seq approach to capture 3'-end of RNAs clearly revealed alternaitve polyadenylation events responsible for reduced muscle mass in AMPK α1, but increased muscle mass in AMPK α2 knockout mice.

2018-05-09 | GSE107212 | GEO

Profiling of alternative transcription start sites and alternative polyadenylation sites in Xenopus tropicalis

Project description:We have developed both WTSS-seq (whole transcriptome start site sequencing) and WTTS-seq (whole transcriptome termini site sequencing) methods to capture either 5’- or 3’-ends of transcripts. HATT-seq (head and tail tag sequencing) is still under development, which can be used to capture both 5’- and 3’ ends of each transcript simultaneously. Iso-seq was used to produce full-length transcripts, which can be used to validate both alternative transcription start sites and alternative polyadenylation sites. CAGE-seq was used to confirm alternative transcription start sites only.

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Genome-wide profiling of Alternative polyadenylation sites in mouse female germline stem cells

Project description:Alternative polyadenylation (APA) is an important post-transcriptional modification implicated in development. Female germline stem cell (FGSC) is unipotent and capable of giving rise to oocyte. However, whether alternative polyadenylation plays a role in self-renew and cell fate determination of FGSCs remain elusive. Here, we used 3T-Seq developed in our lab to profile genome-wide 3a termini of transcripts and delineate APA sites in mouse FGSCs and explored the biological significance of APA modulation in FGSC identity.

2015-11-20 | E-MTAB-4038 | biostudies-arrayexpress

Cancer-specific alternative polyadenylation shapes tumor phenotypes in vivo

Project description:Cancer-specific alternative polyadenylation shapes tumor phenotypes in vivo

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Profiling of alternative transcription start sites and alternative polyadenylation sites in Xenopus tropicalis

Project description:Profiling of alternative transcription start sites and alternative polyadenylation sites in Xenopus tropicalis

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Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns

2016-03-14 | GSE79157 | GEO