Selective nuclear export of specific classes of mRNA from mammalian nuclei is promoted by GANP

نویسندگان

  • Vihandha O. Wickramasinghe
  • Robert Andrews
  • Peter Ellis
  • Cordelia Langford
  • John B. Gurdon
  • Murray Stewart
  • Ashok R. Venkitaraman
  • Ronald A. Laskey
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

mRNA Export from Mammalian Cell Nuclei Is Dependent on GANP

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 ...

متن کامل

Functional and structural characterization of the mammalian TREX-2 complex that links transcription with nuclear messenger RNA export

Export of messenger RNA (mRNA) from the nucleus to the cytoplasm is a critical step in the gene expression pathway of eukaryotic cells. Here, we report the functional and structural characterization of the mammalian TREX-2 complex and show how it links transcription/processing with nuclear mRNA export. Mammalian TREX-2 is based on a germinal-centre associated nuclear protein (GANP) scaffold to ...

متن کامل

Sumoylation is Required for the Cytoplasmic Accumulation of a Subset of mRNAs

In order to discover novel proteins that promote the nuclear export of newly synthesized mRNAs in mammalian cells, we carried out a limited RNAi screen for proteins required for the proper cytoplasmic distribution of a model intronless mRNA. From this screen we obtained two hits, Ubc9 (SUMO-conjugating E2 enzyme) and GANP (germinal center-associated nuclear protein). Depletion of Ubc9 inhibited...

متن کامل

MCM3AP in recessive Charcot-Marie-Tooth neuropathy and mild intellectual disability.

Defects in mRNA export from the nucleus have been linked to various neurodegenerative disorders. We report mutations in the gene MCM3AP, encoding the germinal center associated nuclear protein (GANP), in nine affected individuals from five unrelated families. The variants were associated with severe childhood onset primarily axonal (four families) or demyelinating (one family) Charcot-Marie-Too...

متن کامل

GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy

Somatic hypermutation in B cells is initiated by activation-induced cytidine deaminase-catalyzed C→U deamination at immunoglobulin variable regions. Here we investigate the role of the germinal centre-associated nuclear protein (GANP) in enhancing the access of activation-induced cytidine deaminase (AID) to immunoglobulin variable regions. We show that the nuclear export factor GANP is involved...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 42  شماره 

صفحات  -

تاریخ انتشار 2014