Special Issue "Mechanisms of mRNA Nuclear Export"

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics".

Deadline for manuscript submissions: closed (30 November 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Rozanne M. Sandri-Goldin

Department of Microbiology & Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697, USA
E-Mail
Interests: ICP27; regulatory protein; HSV-1; mRNA processing; RNA export; RNA splicing; virus-host interactions

Special Issue Information

Dear Colleagues,

The journey of an RNA molecule that is destined to be translated into protein begins at its synthesis by RNA polymerase II through processing by the addition of a 5' cap, removal of introns, cleavage and polyadenylation of its 3' end, followed by its transport through nuclear pore complexes (NPC) in the nuclear membrane to reach the cytoplasm where it is translated. Growing evidence has revealed that mRNA export is linked to each of these steps, transcription, 5' capping, splicing and polyadenylation. Major players include the Transcription-Export or TREX complex, which associates with the 5' cap through the Cap Binding Complex; RNA export adaptor proteins like ALYREF and UIF, which form part of the TREX complex and bind to mRNA, and the mRNA receptor protein complex, TAP/NXF and p15, which guides the mRNP through the NPC. Nucleoporins, which line the NPC also play important roles in the transport of the mRNP complex through the NPC. Recent studies have also shown links between alterations in some TREX complex proteins and genome instability. Further, exploration into the functions of nucleoporins or Nups have shown that in addition to their roles in mRNA export, some Nups appear to function in transcription and genome arrangement. Finally, several viruses including the herpesviruses and Influenza virus have evolved mechanisms and encode proteins that hijack cellular mRNA export pathways to favor viral gene expression. Thus, the journey of mRNA from the nucleus to the cytoplasm is complex with many connections along the way.

Prof. Dr. Rozanne M. Sandri-Goldin
Guest Editor

Submission

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Keywords

  • mRNA export
  • Nuclear Pore Complex (NPC)
  • TREX complex
  • TAP/NXF-p15
  • ALYREF
  • UIF
  • Nucleoporins (Nups)
  • mRNA export adaptors

Published Papers (5 papers)

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Research

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Open AccessArticle Sumoylation is Required for the Cytoplasmic Accumulation of a Subset of mRNAs
Genes 2014, 5(4), 982-1000; doi:10.3390/genes5040982
Received: 6 August 2014 / Revised: 26 September 2014 / Accepted: 4 October 2014 / Published: 20 October 2014
Cited by 2 | PDF Full-text (7833 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
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
[...] Read more.
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 the proper cytoplasmic distribution of certain overexpressed intronless mRNAs, while depletion of GANP affected all tested mRNAs. Depletion of Sae1, which is also required for sumoylation, partially inhibited the cytoplasmic distribution of our model mRNA. Interestingly, the block in cytoplasmic accumulation in Ubc9-depleted cells could be overcome if an intron was incorporated into the mRNA. Surprisingly, Ubc9-depleted cells had normal nuclear export of newly synthesized intronless mRNAs, indicating that the observed accumulation of the model mRNA in the nuclei of transfected cells was likely due to some more general perturbation. Indeed, depletion of Ubc9, coupled with the overexpression of the intronless mRNAs, caused the redistribution of the nuclear speckle protein SC35 to cytoplasmic foci. Our results suggest that sumoylation may play a role in the proper assembly of mRNPs and/or the distribution of key RNA binding proteins, and may thus contribute to general protein expression patterns. Full article
(This article belongs to the Special Issue Mechanisms of mRNA Nuclear Export)

Review

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Open AccessReview Nuclear Export of Messenger RNA
Genes 2015, 6(2), 163-184; doi:10.3390/genes6020163
Received: 30 January 2015 / Revised: 23 March 2015 / Accepted: 24 March 2015 / Published: 31 March 2015
Cited by 4 | PDF Full-text (13598 KB) | HTML Full-text | XML Full-text
Abstract
Transport of messenger RNA (mRNA) from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the
[...] Read more.
Transport of messenger RNA (mRNA) from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP) particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex. Full article
(This article belongs to the Special Issue Mechanisms of mRNA Nuclear Export)
Open AccessReview RNA Export through the NPC in Eukaryotes
Genes 2015, 6(1), 124-149; doi:10.3390/genes6010124
Received: 28 November 2014 / Revised: 27 February 2015 / Accepted: 10 March 2015 / Published: 20 March 2015
Cited by 8 | PDF Full-text (11873 KB) | HTML Full-text | XML Full-text
Abstract
In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear
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In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC. Full article
(This article belongs to the Special Issue Mechanisms of mRNA Nuclear Export)
Open AccessReview Three-Dimensional Mapping of mRNA Export through the Nuclear Pore Complex
Genes 2014, 5(4), 1032-1049; doi:10.3390/genes5041032
Received: 15 August 2014 / Revised: 2 October 2014 / Accepted: 20 October 2014 / Published: 11 November 2014
Cited by 2 | PDF Full-text (11287 KB) | HTML Full-text | XML Full-text
Abstract
The locations of transcription and translation of mRNA in eukaryotic cells are spatially separated by the nuclear envelope (NE). Plenty of nuclear pore complexes (NPCs) embedded in the NE function as the major gateway for the export of transcribed mRNAs from the nucleus
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The locations of transcription and translation of mRNA in eukaryotic cells are spatially separated by the nuclear envelope (NE). Plenty of nuclear pore complexes (NPCs) embedded in the NE function as the major gateway for the export of transcribed mRNAs from the nucleus to the cytoplasm. Whereas the NPC, perhaps one of the largest protein complexes, provides a relatively large channel for macromolecules to selectively pass through it in inherently three-dimensional (3D) movements, this channel is nonetheless below the diffraction limit of conventional light microscopy. A full understanding of the mRNA export mechanism urgently requires real-time mapping of the 3D dynamics of mRNA in the NPC of live cells with innovative imaging techniques breaking the diffraction limit of conventional light microscopy. Recently, super-resolution fluorescence microscopy and single-particle tracking (SPT) techniques have been applied to the study of nuclear export of mRNA in live cells. In this review, we emphasize the necessity of 3D mapping techniques in the study of mRNA export, briefly summarize the feasibility of current 3D imaging approaches, and highlight the new features of mRNA nuclear export elucidated with a newly developed 3D imaging approach combining SPT-based super-resolution imaging and 2D-to-3D deconvolution algorithms. Full article
(This article belongs to the Special Issue Mechanisms of mRNA Nuclear Export)
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Open AccessReview Regulation of mRNA Trafficking by Nuclear Pore Complexes
Genes 2014, 5(3), 767-791; doi:10.3390/genes5030767
Received: 25 July 2014 / Revised: 25 August 2014 / Accepted: 26 August 2014 / Published: 2 September 2014
Cited by 13 | PDF Full-text (10614 KB) | HTML Full-text | XML Full-text
Abstract
Over the last two decades, multiple studies have explored the mechanisms governing mRNA export out of the nucleus, a crucial step in eukaryotic gene expression. During transcription and processing, mRNAs are assembled into messenger ribonucleoparticles (mRNPs). mRNPs are then exported through nuclear pore
[...] Read more.
Over the last two decades, multiple studies have explored the mechanisms governing mRNA export out of the nucleus, a crucial step in eukaryotic gene expression. During transcription and processing, mRNAs are assembled into messenger ribonucleoparticles (mRNPs). mRNPs are then exported through nuclear pore complexes (NPCs), which are large multiprotein assemblies made of several copies of a limited number of nucleoporins. A considerable effort has been put into the dissection of mRNA export through NPCs at both cellular and molecular levels, revealing the conserved contributions of a subset of nucleoporins in this process, from yeast to vertebrates. Several reports have also demonstrated the ability of NPCs to sort out properly-processed mRNPs for entry into the nuclear export pathway. Importantly, changes in mRNA export have been associated with post-translational modifications of nucleoporins or changes in NPC composition, depending on cell cycle progression, development or exposure to stress. How NPC modifications also impact on cellular mRNA export in disease situations, notably upon viral infection, is discussed. Full article
(This article belongs to the Special Issue Mechanisms of mRNA Nuclear Export)
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