title: Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns.
abstract: 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 in HeLa cells 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.
authors.affiliation: a Department of Microbiology and Molecular Genetics , School of Medicine, University of California , Irvine , CA , USA.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Movassat
authors.affiliation: b Institute of Molecular Biology (IMB) , Mainz , Germany.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Crabb
authors.affiliation: a Department of Microbiology and Molecular Genetics , School of Medicine, University of California , Irvine , CA , USA.|b Institute of Molecular Biology (IMB) , Mainz , Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Busch
authors.affiliation: a Department of Microbiology and Molecular Genetics , School of Medicine, University of California , Irvine , CA , USA.
authors.forename: Chengguo
authors.initials: C
authors.lastname: Yao
authors.affiliation: a Department of Microbiology and Molecular Genetics , School of Medicine, University of California , Irvine , CA , USA.
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Reynolds
authors.affiliation: a Department of Microbiology and Molecular Genetics , School of Medicine, University of California , Irvine , CA , USA.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Shi
authors.affiliation: a Department of Microbiology and Molecular Genetics , School of Medicine, University of California , Irvine , CA , USA.
authors.forename: Klemens J
authors.initials: KJ
authors.lastname: Hertel
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D006367:HeLa Cells; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007438:Introns / Q000502:physiology*; D026723:Polyadenylation / Q000502:physiology*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D039221:mRNA Cleavage and Polyadenylation Factors
keywords: Alternative polyadenylation; CFIm25; CstF64; HnRNP A2/B1; PAS-Seq; RNA-Seq; alternative splicing