Characterisation of a novel vertebrate mRNA export pathway
Lead Research Organisation:
University of Sheffield
Department Name: Molecular Biology and Biotechnology
Abstract
A human cell contains a specialised compartment called the nucleus which holds DNA and this is surrounded by the cytoplasm. Sections of the DNA known as genes carry the information to make proteins which are one of the principal building blocks in humans. In the nucleus, copies of genes are made called messenger RNA which then have to be moved from the nucleus through a special hole called the nuclear pore, to the cytoplasm. In the cytoplasm, mRNA is decoded to make proteins. We have discovered a new pathway for moving messenger from the nucleus, through the nuclear pores to the cytoplasm which uses a protein called UIF. In this proposal we will identify other proteins which interact with UIF and investigate how they bind to UIF. We will also investigate how UIF moves around in the cell and how UIF performs its functions in the transport of messenger RNA. These studies will help us understand how genes are turned into proteins in human cells.
Technical Summary
We have identified a new mRNA export factor in human cells. In this project we will characterise the dynamics of this protein, the effects of post-translational modifications on its function and characterise its binding partners.
Organisations
People |
ORCID iD |
Stuart Wilson (Principal Investigator) |
Publications
Cruz-Migoni A
(2011)
A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.
in Science (New York, N.Y.)
Dufu K
(2010)
ATP is required for interactions between UAP56 and two conserved mRNA export proteins, Aly and CIP29, to assemble the TREX complex
in Genes & Development
Hautbergue GM
(2009)
UIF, a New mRNA export adaptor that works together with REF/ALY, requires FACT for recruitment to mRNA.
in Current biology : CB
Hautbergue GM
(2012)
BLF1, the first Burkholderia pseudomallei toxin, connects inhibition of host protein synthesis with melioidosis.
in Biochemical Society transactions
Hung ML
(2010)
Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1.
in Nucleic acids research
Jackson BR
(2011)
An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export.
in PLoS pathogens
Tunnicliffe RB
(2011)
Structural basis for the recognition of cellular mRNA export factor REF by herpes viral proteins HSV-1 ICP27 and HVS ORF57.
in PLoS pathogens
Viphakone N
(2012)
TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export.
in Nature communications
Viphakone N
(2015)
Luzp4 defines a new mRNA export pathway in cancer cells.
in Nucleic acids research
Description | 1. A new mRNA export factor called UIF and how it works in mRNA export. 2. A new mRNA export factor called CIP29 and how it works in mRNA export. 3. The first ever toxin identified from the bacterial pathogen Burkholderia pseudomallei and shpwn how it works to block translation in mammalian cells. 4. Discovered how the TREX complex flips open Nxf1 to license mRNA for export from the nucleus. 5. Discovered how arginine methylation of Alyref allows it to hand mRNA over to Nxf1 during mRNA export. 6. Determined the structures of Herpes viral proteins and how they interaxct with a mammlian mRNA export factor. 7. Showed that the UIF protein is used by Herpes viruses for export of viral transcripts. |
Exploitation Route | The structural studies on the Herpes viral proteins may lead to new inhibitors of viral replication. The identification of a BLF1 toxin from Burkholderia may open new avenues for diagnosis and treatment of melliodosis. |
Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |