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Dynamic regulation of cleavage and polyadenylation in differentiation and development (225.3)
Author(s) -
Tian Bin
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.225.3
Subject(s) - polyadenylation , gene isoform , gene knockdown , exon , biology , cellular differentiation , gene , untranslated region , cleavage (geology) , genetics , gene expression , regulation of gene expression , coding region , microbiology and biotechnology , messenger rna , paleontology , fracture (geology)
Transcripts of most mammalian genes display alternative cleavage and polyadenylation (APA). Sites of APA (pAs) located in the 3’‐most exon typically lead to mRNA isoforms with different 3’ untranslated regions (3’UTRs), and those located in upstream introns or exons also cause different coding sequences. We previously reported a general trend of relative upregulation of promoter‐distal pA isoforms during cell differentiation and embryonic development. Here we examined different cell differentiation systems with 3’READS, a recently developed deep sequencing method to analyze APA isoform expression. We identified cell type‐specific, and differentiation‐specific APA events, and examined ontologies of genes regulated at the APA level. We analyzed how APA is related to overall gene expression. We have found that APA is an important layer of gene regulation, impacting cell identity and differentiation state. In addition, to understand the role of core cleavage and polyadenylation factors (called C/P factors) in APA, we carried out a global knockdown of expression of C/P factors and examined how APA changes in response to C/P factor perturbation is related to APA regulation in cell differentiation.