GANP enhances the efficiency of mRNA nuclear export in mammalian cells

Abstract

N uclear 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.

Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions

“…However, data from D. melano gaster suggest that in flies SAGA also couples efficient transcription and RNA export to the NPC 82 , and TREX2 orthologues promote the association of TREX-THO to mRNA 93 . Furthermore, a TREX2 homologue, which also binds to NUPs, has also been identified in Arabidopsis thaliana 94 , and human TREX2 has been shown to facilitate the movement of mRNAs from transcriptiona l foci to the nuclear periphery 95 . Furthermore, NPCs have been shown to modulate gene expression by promoting the assembly and/or maintenance of gene loops (FIG.…”

Aiding and abetting cancer: mRNA export and the nuclear pore

“…The germinal centre associated protein (GANP), a constituent of the TREX-2 complex is highly elevated in mantle cell, diffuse large B cell and Hodgkin’ s lymphomas [47]. Although initial observations suggested a more general role for GANP in bulk mRNA export [48], a recent report suggests that depletion of GANP in human cells may inhibit export of specific mRNAs [49]. In either case, GANP elevation in tumors likely drives expression of a subset of transcripts by increasing recruitment of the corresponding cargo mRNPs to the nuclear basket thereby increasing export efficiency.…”

Three-Dimensional Mapping of mRNA Export through the Nuclear Pore Complex

“…However, the exact causes for the abortive nuclear export events of mRNA are not completely understood yet. Current accumulation of evidence suggest several possible reasons including the remodeling and preparation of mRNP for transport by cofactors and adaptor proteins such as TREX, TREX-2 and GANP at the nucleoplasmic face of the NPC, the physical constrain for mRNP particles at the narrowest scaffold region of the NPC and the dissociation process involving Dbp5 and Gle1 on the cytoplasmic side of the NPC [ 30 , 32 , 34 , 111 , 112 , 113 ]. Second, a refined nuclear export time of ~12 ms for mRNPs was obtained.…”