title: Sac3 is an mRNA export factor that localizes to cytoplasmic fibrils of nuclear pore complex.
abstract: In eukaryotes, mRNAs are transcribed in the nucleus and exported to the cytoplasm for translation to occur. Messenger RNAs complexed with proteins referred to as ribonucleoparticles are recognized for nuclear export in part by association with Mex67, a key Saccharomyces cerevisiae mRNA export factor and homolog of human TAP/NXF1. Mex67, along with its cofactor Mtr2, is thought to promote ribonucleoparticle translocation by interacting directly with components of the nuclear pore complex (NPC). Herein, we show that the nuclear pore-associated protein Sac3 functions in mRNA export. Using a mutant allele of MTR2 as a starting point, we have identified a mutation in SAC3 in a screen for synthetic lethal interactors. Loss of function of SAC3 causes a strong nuclear accumulation of mRNA and synthetic lethality with a number of mRNA export mutants. Furthermore, Sac3 can be coimmunoprecipitated with Mex67, Mtr2, and other factors involved in mRNA export. Immunoelectron microscopy analysis shows that Sac3 localizes exclusively to cytoplasmic fibrils of the NPC. Finally, Mex67 accumulates at the nuclear rim when SAC3 is mutated, suggesting that Sac3 functions in Mex67 translocation through the NPC.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Elissa P
authors.initials: EP
authors.lastname: Lei
authors.forename: Charlene A
authors.initials: CA
authors.lastname: Stern
authors.forename: Birthe
authors.initials: B
authors.lastname: Fahrenkrog
authors.forename: Heike
authors.initials: H
authors.lastname: Krebber
authors.forename: Terence I
authors.initials: TI
authors.lastname: Moy
authors.forename: Ueli
authors.initials: U
authors.lastname: Aebi
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Silver
mesh_terms: D001692:Biological Transport / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D022022:Nuclear Pore / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism; D018272:Porins; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C106898:MEX67 protein, S cerevisiae; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D018272:Porins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C103382:SAC3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins