title: Pre-mRNA splicing and mRNA export linked by direct   interactions between UAP56 and Aly.
abstract: Recent studies indicate that splicing of pre-messenger RNA and export of mRNA are normally coupled in vivo. During splicing, the conserved mRNA export factor Aly is recruited to the spliced mRNA-protein complex (mRNP), which targets the mRNA for export. At present, it is not known how Aly is recruited to the spliced mRNP. Here we show that the conserved DEAD-box helicase UAP56, which functions during spliceosome assembly, interacts directly and highly specifically with Aly. Moreover, UAP56 is present together with Aly in the spliced mRNP. Significantly, excess UAP56 is a potent dominant negative inhibitor of mRNA export. Excess UAP56 also inhibits the recruitment of Aly to the spliced mRNP. Furthermore, a mutation in Aly that blocks its interaction with UAP56 prevents recruitment of Aly to the spliced mRNP. These data suggest that the splicing factor UAP56 functions in coupling the splicing and export machineries by recruiting Aly to the spliced mRNP.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Luo
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: K
authors.initials: K
authors.lastname: Magni
authors.forename: C
authors.initials: C
authors.lastname: Christoforides
authors.forename: J
authors.initials: J
authors.lastname: Rappsilber
authors.forename: M
authors.initials: M
authors.lastname: Mann
authors.forename: R
authors.initials: R
authors.lastname: Reed
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000378:metabolism; D017381:Spliceosomes / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D014981:Xenopus
chemical_list: C105242:ALYREF protein, human; D009687:Nuclear Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C027900:RNA-dependent ATPase