Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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CPEB inducible knock-down in a H.D. Myz cell line

ABSTRACT: Messenger RNA stability, localization, and translation are largely determined by sequences in their 3M-bM-^@M-2 untranslated regions (3M-bM-^@M-^YUTRs), which recruit regulatory proteins and RNAs. More than half of the mammalian genes generate multiple mRNA isoforms differing in their 3M-bM-^@M-2UTRs and therefore in their regulatory elements. The Cytoplasmic Polyadenylation Element Binding protein 1 (CPEB1) binds to cognate sites in 3M-bM-^@M-^Y UTRs and regulates translation. CPEB1 can shuttle to the nucleus and we report its co-localization with splicing factors. CPEB1 knock down leads to changes in alternative splicing, and we show that alternative 3M-bM-^@M-^Y splice site linked to alternative polyadenylation of the bub-3 pre-mRNA, important for cell proliferation, is regulated by CPEB1 at least in part by preventing 3M-bM-^@M-^Y splice site recognition by U2AF. RNA-Seq experiments reveal that CPEB1 mediates 3M-bM-^@M-^Y UTR shortening of hundreds of mRNAs, leading to changes in their translation efficiency. Three total RNA from three biological replicates were labeled and hybridized versus its own control in direct and dye-swap hybridizations.

ORGANISM(S): Homo sapiens

SUBMITTER: BELEN MINANA

PROVIDER: E-GEOD-32440 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

CPEB1 coordinates alternative 3'-UTR formation with translational regulation.

Bava Felice-Alessio FA Eliscovich Carolina C Ferreira Pedro G PG Miñana Belen B Ben-Dov Claudia C Guigó Roderic R Valcárcel Juan J Méndez Raúl R

Nature 20130224 7439

More than half of mammalian genes generate multiple messenger RNA isoforms that differ in their 3' untranslated regions (3' UTRs) and therefore in regulatory sequences, often associated with cell proliferation and cancer; however, the mechanisms coordinating alternative 3'-UTR processing for specific mRNA populations remain poorly defined. Here we report that the cytoplasmic polyadenylation element binding protein 1 (CPEB1), an RNA-binding protein that regulates mRNA translation, also controls a ...[more]

PMID: 23434754

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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

Dataset Information

CPEB inducible knock-down in a H.D. Myz cell line

Publications

CPEB1 coordinates alternative 3'-UTR formation with translational regulation.

Similar Datasets

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