mRNA export from mammalian cell nuclei is dependent on GANP
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Updated: Jun 17, 2026

Analysis of mRNA Nuclear Export Kinetics in Mammalian Cells by Microinjection
Published on: December 4, 2010
Vihandha O Wickramasinghe1, Paul I A McMurtrie, Anthony D Mills
1MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 0XZ, UK. vw222@hutchison-mrc.cam.ac.uk
Abstract:
Bulk nuclear export of messenger ribonucleoproteins (mRNPs) through nuclear pore complexes (NPCs) is mediated by NXF1. It binds mRNPs through adaptor proteins such as ALY and SR splicing factors and mediates translocation through the central NPC transport channel via transient interactions with FG nucleoporins. Here, we show that mammalian cells require GANP (germinal center-associated nuclear protein) for efficient mRNP nuclear export and for efficient recruitment of NXF1 to NPCs. Separate regions of GANP show local homology to FG nucleoporins, the yeast mRNA export factor Sac3p, and the mammalian MCM3 acetyltransferase. GANP interacts with both NXF1 and NPCs and partitions between NPCs and the nuclear interior. GANP depletion inhibits mRNA export, with retention of mRNPs and NXF1 in punctate foci within the nucleus. The GANP N-terminal region that contains FG motifs interacts with the NXF1 FG-binding domain. Overexpression of this GANP fragment leads to nuclear accumulation of both poly(A)(+)RNA and NXF1. Treatment with transcription inhibitors redistributes GANP from NPCs into foci throughout the nucleus. These results establish GANP as an integral component of the mammalian mRNA export machinery and suggest a model whereby GANP facilitates the transfer of NXF1-containing mRNPs to NPCs.
Insights
Germinal center-associated nuclear protein (GANP) is essential for efficient mRNA nuclear export in mammalian cells. GANP facilitates the recruitment of NXF1 to nuclear pore complexes, ensuring proper messenger ribonucleoprotein export.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Nuclear pore complexes (NPCs) regulate transport between the nucleus and cytoplasm.
- Bulk nuclear export of messenger ribonucleoproteins (mRNPs) is primarily mediated by the NXF1 pathway.
- Adaptor proteins like ALY and SR splicing factors facilitate mRNP binding to NXF1.
Purpose of the Study:
- To investigate the role of germinal center-associated nuclear protein (GANP) in mammalian mRNA nuclear export.
- To determine GANP's interaction with the NXF1 export machinery and NPCs.
- To elucidate GANP's contribution to the mRNP translocation process.
Main Methods:
- Depletion of GANP in mammalian cells.
- Analysis of mRNP and NXF1 localization using microscopy.
- Biochemical assays to study protein interactions (GANP, NXF1, NPCs).
- Functional studies involving GANP fragment overexpression and transcription inhibition.
Main Results:
- GANP is required for efficient mRNP nuclear export and NXF1 recruitment to NPCs.
- GANP depletion leads to nuclear retention of mRNPs and NXF1 in punctate foci.
- GANP interacts with NXF1 and NPCs, with specific FG motifs mediating interaction with NXF1.
- Overexpression of a GANP fragment causes nuclear accumulation of poly(A)(+)RNA and NXF1.
Conclusions:
- GANP is an integral component of the mammalian mRNA export machinery.
- GANP facilitates the transfer of NXF1-containing mRNPs to NPCs.
- GANP acts as a crucial link between mRNPs and the NPC transport channel.
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