Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional activity regulates alternative cleavage and polyadenylation

ABSTRACT: Genes containing multiple polyadenylation (polyA) sites express mRNA isoforms with variable 3’ untranslated regions (3’UTRs). We found that short and long 3’UTR isoforms were relatively more abundant when genes were highly and lowly expressed, respectively, in human and mouse cells. Consistently, upregulated and downregulated genes were more likely to have shortened and lengthened 3’UTRs, respectively, when genes changed expression under different cell conditions or in response to extracellular stimuli. Using nuclear run-on assays, we found that RNA polymerase II (Pol II) was more likely to pause at the polyA site of highly expressed genes than that of lowly expressed ones. Moreover, in line with the difference in polyA site usage, highly expressed genes tend to have higher H3K4me3 and H3K36me3 levels but a lower density of nucleosome around promoter-proximal polyA sites relative to distal ones. Taken together, our results indicate that the efficiency of 3’ end processing is generally coupled to transcriptional activity, leading to modulation of polyA site choice by transcription and thus connecting transcriptional control with post-transcriptional regulation via pre-mRNA processing. Nascent RNA sequencing of C2C12 cell

ORGANISM(S): Mus musculus

SUBMITTER: Zhe Ji

PROVIDER: E-GEOD-26512 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptional activity regulates alternative cleavage and polyadenylation.

Ji Zhe Z Luo Wenting W Li Wencheng W Hoque Mainul M Pan Zhenhua Z Zhao Yun Y Tian Bin B

Molecular systems biology 20110927

Genes containing multiple pre-mRNA cleavage and polyadenylation sites, or polyA sites, express mRNA isoforms with variable 3' untranslated regions (UTRs). By systematic analysis of human and mouse transcriptomes, we found that short 3'UTR isoforms are relatively more abundant when genes are highly expressed whereas long 3'UTR isoforms are relatively more abundant when genes are lowly expressed. Reporter assays indicated that polyA site choice can be modulated by transcriptional activity through ...[more]

PMID: 21952137

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Project description:Our computational analyses of sequencing depth and the discovery rates of sequence elements in the 3’UTR strongly demonstrate that interrogation of the 3’UTRome in specific tissues and cell types across development will greatly expand the identification of new 3’UTR isoforms and the sequence elements therein. Therefore, we will generate and sequence the 3’UTRs from the cell types isolated from the developing germline, mature germ cells, and early embryogenesis. In addition, we will identify the 3’UTRs for the transcripts isolated from the major somatic tissues during late- and post-embryonic development. Based on our sequencing estimates, we anticipate that the tissue-specific interrogation of the 3’UTRome will reveal a far greater diversity of novel 3’UTR isoform expression that is masked in the whole-worm 3’UTRome sequence data. Using the transgenic myo-3::PABP strain, we have generated polyA-captured libraries for late embryos and across the major stages of post-embryonic development for the muscle transcriptome. We propose to generate these polyA-captured libraries for transcripts expressed in the other major tissues across development. PolyA-captured libraries will be generated for deep sequencing following the tissue-specific isolation of mRNAs by PABP pulldowns (the PABP immunoprecipitations will take advantage of a FLAG epitope which is fused to PABP in all of the transgenic strains). We propose to validate the expression of tissue- specific transcripts by qPCR for select transcripts known to be expressed in those particular tissues. In addition, following the strategy we have employed for the large-scale polyA-captured libraries from muscle, we will perform quality checks for 3ʼ end capture by manually sequencing ~60 clones isolated from each library. Once we have obtained the deep sequencing data, we will analyze all of the sequence reads using the bioinformatics pipeline that we established for the whole-worm polyA- captured sequences (Mangone et al., 2010).

Dataset Information

Transcriptional activity regulates alternative cleavage and polyadenylation

Publications

Transcriptional activity regulates alternative cleavage and polyadenylation.

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