MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Biomedical Campus, Cambridge CB2 0XZ, UK, The Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK, Wellcome Trust, Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK and Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
Nucleic Acids Res. 2014 Apr;42(8):5059-71. doi: 10.1093/nar/gku095. Epub 2014 Feb 7.
The nuclear phase of the gene expression pathway culminates in the export of mature messenger RNAs (mRNAs) to the cytoplasm through nuclear pore complexes. GANP (germinal- centre associated nuclear protein) promotes the transfer of mRNAs bound to the transport factor NXF1 to nuclear pore complexes. Here, we demonstrate that GANP, subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex, promotes selective nuclear export of a specific subset of mRNAs whose transport depends on NXF1. Genome-wide gene expression profiling showed that half of the transcripts whose nuclear export was impaired following NXF1 depletion also showed reduced export when GANP was depleted. GANP-dependent transcripts were highly expressed, yet short-lived, and were highly enriched in those encoding central components of the gene expression machinery such as RNA synthesis and processing factors. After injection into Xenopus oocyte nuclei, representative GANP-dependent transcripts showed faster nuclear export kinetics than representative transcripts that were not influenced by GANP depletion. We propose that GANP promotes the nuclear export of specific classes of mRNAs that may facilitate rapid changes in gene expression.
基因表达途径的核相最终导致成熟信使 RNA(mRNA)通过核孔复合物向细胞质的输出。GANP(生殖中心相关核蛋白)促进与运输因子 NXF1 结合的 mRNAs 转移到核孔复合物。在这里,我们证明,GANP 是转录-输出-2(TREX-2)mRNA 输出复合物的亚基,可促进特定子集的 mRNA 的选择性核输出,这些 mRNA 的运输依赖于 NXF1。全基因组基因表达谱分析表明,在 NXF1 耗尽后,其核输出受到抑制的一半转录本在 GANP 耗尽时的输出也减少。依赖 GANP 的转录本表达水平较高,但寿命较短,并且富含 RNA 合成和加工因子等基因表达机器的核心成分。将代表性的 GANP 依赖的转录本注射到非洲爪蟾卵母细胞核后,其核输出动力学比不受 GANP 耗尽影响的代表性转录本更快。我们提出,GANP 促进了特定种类的 mRNA 的核输出,这可能有助于快速改变基因表达。