UIF, a New mRNA Export Adaptor that Works Together with REF/ALY, Requires FACT for Recruitment to mRNA

Abstract

Messenger RNA (mRNA) export adaptors play an important role in the transport of mRNA from the nucleus to the cytoplasm. They couple early mRNA processing events such as 5′ capping and 3′ end formation with loading of the TAP/NXF1 export receptor onto mRNA. The canonical adaptor REF/ALY/Yra1 is recruited to mRNA via UAP56 and subsequently delivers the mRNA to NXF1 [1Carmody S.R. Wente S.R. mRNA nuclear export at a glance.J. Cell Sci. 2009; 122: 1933-1937Crossref PubMed Scopus (181) Google Scholar]. Knockdown of UAP56 [2MacMorris M. Brocker C. Blumenthal T. UAP56 levels affect viability and mRNA export in Caenorhabditis elegans.RNA. 2003; 9: 847-857Crossref PubMed Scopus (77) Google Scholar, 3Gatfield D. Le Hir H. Schmitt C. Braun I.C. Kocher T. Wilm M. Izaurralde E. The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila.Curr. Biol. 2001; 11: 1716-1721Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar] and NXF1 [4Herold A. Klymenko T. Izaurralde E. NXF1/p15 heterodimers are essential for mRNA nuclear export in Drosophila.RNA. 2001; 7: 1768-1780PubMed Google Scholar, 5Wilkie G.S. Zimyanin V. Kirby R. Korey C. Francis-Lang H. Van Vactor D. Davis I. Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development.RNA. 2001; 7: 1781-1792PubMed Google Scholar, 6Herold A. Teixeira L. Izaurralde E. Genome-wide analysis of nuclear mRNA export pathways in Drosophila.EMBO J. 2003; 22: 2472-2483Crossref PubMed Scopus (134) Google Scholar, 7Williams B.J. Boyne J.R. Goodwin D.J. Roaden L. Hautbergue G.M. Wilson S.A. Whitehouse A. The prototype gamma-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA via the cellular mRNA export pathway.Biochem. J. 2005; 387: 295-308Crossref PubMed Scopus (62) Google Scholar] in higher eukaryotes efficiently blocks mRNA export, whereas knockdown of REF only causes a modest reduction, suggesting the existence of additional adaptors [8Gatfield D. Izaurralde E. REF1/Aly and the additional exon junction complex proteins are dispensable for nuclear mRNA export.J. Cell Biol. 2002; 159: 579-588Crossref PubMed Scopus (170) Google Scholar, 9Longman D. Johnstone I.L. Caceres J.F. The Ref/Aly proteins are dispensable for mRNA export and development in Caenorhabditis elegans.RNA. 2003; 9: 881-891Crossref PubMed Scopus (87) Google Scholar, 10Katahira J. Inoue H. Hurt E. Yoneda Y. Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA.EMBO J. 2009; 28: 556-567Crossref PubMed Scopus (109) Google Scholar]. Here we identify a new UAP56-interacting factor, UIF, which functions as an export adaptor, binding NXF1 and delivering mRNA to the nuclear pore. REF and UIF are simultaneously found on the same mRNA molecules, and both proteins are required for efficient export of mRNA. We show that the histone chaperone FACT specifically binds UIF, but not REF, via the SSRP1 subunit, and this interaction is required for recruitment of UIF to mRNA. Together the results indicate that REF and UIF represent key human adaptors for the export of cellular mRNAs via the UAP56-NXF1 pathway.