title: GANP enhances the efficiency of mRNA nuclear export in mammalian cells.
abstract: Nuclear export of mRNPs is mediated by transport factors such as NXF1 that bind mRNPs and mediate their translocation through the central channel of nuclear pores (NPC) using transient interactions with FG-nucleoporins. A number of nuclear factors enhance the efficiency of this process by concentrating mRNPs at the nuclear face of the pores. Although this enhancement has been explored mainly with the yeast TREX-2 complex, recent work has indicated that mammalian cells employ GANP (Germinal-centre Associated Nuclear Protein) for efficient mRNP nuclear export and for efficient recruitment of NXF1-containing mRNPs to NPCs. GANP is constructed from several domains that show local homology to FG-nucleoporins, the yeast mRNA export factor Sac3p and the mammalian MCM3 acetyltransferase. Whereas yeast TREX-2 is located primarily at nuclear pores, some GANP is located in the nuclear interior in addition to that found at the pores. GANP depletion inhibits bulk mRNA export, resulting in retention of mRNPs and NXF1 in punctate foci within the nucleoplasm, consistent with GANP's being an integral component of the mammalian mRNA export machinery. Here, we discuss the model for GANP function presented in our recent paper and its implications for the mechanism of mRNA export in mammalian cells.
authors.affiliation: MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge, UK. vw222@hutchison-mrc.cam.ac.uk
authors.forename: Vihandha O
authors.initials: VO
authors.lastname: Wickramasinghe
authors.forename: Murray
authors.initials: M
authors.lastname: Stewart
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Laskey
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D008322:Mammals; D008954:Models, Biological; D022022:Nuclear Pore / Q000737:chemistry / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism; D034443:RNA Transport / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein; D000123:Acetyltransferases