Dataset Information

APADB: a database for alternative polyadenylation and microRNA regulation events.

ABSTRACT: Alternative polyadenylation (APA) is a widespread mechanism that contributes to the sophisticated dynamics of gene regulation. Approximately 50% of all protein-coding human genes harbor multiple polyadenylation (PA) sites; their selective and combinatorial use gives rise to transcript variants with differing length of their 3' untranslated region (3'UTR). Shortened variants escape UTR-mediated regulation by microRNAs (miRNAs), especially in cancer, where global 3'UTR shortening accelerates disease progression, dedifferentiation and proliferation. Here we present APADB, a database of vertebrate PA sites determined by 3' end sequencing, using massive analysis of complementary DNA ends. APADB provides (A)PA sites for coding and non-coding transcripts of human, mouse and chicken genes. For human and mouse, several tissue types, including different cancer specimens, are available. APADB records the loss of predicted miRNA binding sites and visualizes next-generation sequencing reads that support each PA site in a genome browser. The database tables can either be browsed according to organism and tissue or alternatively searched for a gene of interest. APADB is the largest database of APA in human, chicken and mouse. The stored information provides experimental evidence for thousands of PA sites and APA events. APADB combines 3' end sequencing data with prediction algorithms of miRNA binding sites, allowing to further improve prediction algorithms. Current databases lack correct information about 3'UTR lengths, especially for chicken, and APADB provides necessary information to close this gap. Database URL: http://tools.genxpro.net/apadb/.

SUBMITTER: Muller S

PROVIDER: S-EPMC4105710 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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APADB: a database for alternative polyadenylation and microRNA regulation events.

Müller Sören S Rycak Lukas L Afonso-Grunz Fabian F Winter Peter P Zawada Adam M AM Damrath Ewa E Scheider Jessica J Schmäh Juliane J Koch Ina I Kahl Günter G Rotter Björn B

Database : the journal of biological databases and curation 20140722

Alternative polyadenylation (APA) is a widespread mechanism that contributes to the sophisticated dynamics of gene regulation. Approximately 50% of all protein-coding human genes harbor multiple polyadenylation (PA) sites; their selective and combinatorial use gives rise to transcript variants with differing length of their 3' untranslated region (3'UTR). Shortened variants escape UTR-mediated regulation by microRNAs (miRNAs), especially in cancer, where global 3'UTR shortening accelerates disea ...[more]

PMID: 25052703

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Project description:Background:Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. microRNAs (miRNAs) repress gene expression by binding to complementary sequences in the 3' untranslated region (3'UTR) of target mRNAs. Alternative polyadenylation (APA) are relevant to the variability of the 3'UTR of mRNA. However, the posttranscriptional dysregulation of miRNAs and APA in CRC are poorly understood. Method:In this study, we conducted small RNA sequencing to identify differentially expressed miRNAs (DERs) and their target genes. Function analysis on DER-target genes can explain the regulation roles of miRNAs in CRC. The mutual regulation of miRNAs and APA was analyzed by combining miRNA data to 3'UTR alteration using 3' termini of polyadenylated RNAs sequencing (3T-seq) technique, and this was validated using TCGA gene expression data. Results:Our results showed 64 significant differentially expressed miRNAs (DERs) in CRC patients. Their target genes were related to cell adhesion and transcription regulation and were prevailingly involved in the CRC-related pathway. Integrative analysis of the miRNA and APA profile revealed 16 DERs were correlated with 12 polyadenylation factors, and six of them were significantly differently expressed in CRC. We also found four DERs that lost binding sites due to APA and showed a positive correlation between the miRNA and gene expression. Conclusion:Our study found that miRNAs regulated APA by modulating key polyadenylation factors, and several miRNAs lost their suppression on mRNA due to APA. Associating this with gene expression may provide some important clues for a deeper study of posttranscriptional cellular regulation and biomarker research in CRC. Our data provided the first evidence that the interaction between miRNAs and APA associated with gene expression could serve as biomarkers for CRC, suggesting that hsa-miR-133a-3p and MLEC, hsa-miR-145-5p and SET, hsa-miR-1-3p and PPIA, and hsa-miR-378d and YY1 might be novel and potential biomarkers in improving the diagnosis of CRC.

Dataset Information

APADB: a database for alternative polyadenylation and microRNA regulation events.

Publications

APADB: a database for alternative polyadenylation and microRNA regulation events.

Similar Datasets

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