Abstract
Cancer testis antigens (CTAs) represented a poorly characterized group of proteins whose expression is normally restricted to testis but are frequently up-regulated in cancer cells. Here we show that one CTA, Luzp4, is an mRNA export adaptor. It associates with the TREX mRNA export complex subunit Uap56 and harbours a Uap56 binding motif, conserved in other mRNA export adaptors. Luzp4 binds the principal mRNA export receptor Nxf1, enhances its RNA binding activity and complements Alyref knockdown in vivo. Whilst Luzp4 is up-regulated in a range of tumours, it appears preferentially expressed in melanoma cells where it is required for growth.
Highlights
The transport of mRNA from the nucleus to the cytoplasm is an essential step in eukaryotic gene expression
We examined the ability of GFPLuzp4 expression to suppress up-regulation of export factors following Alyref+Uif RNAi and found that it could not (Figure 5, lanes 34–36). These results indicate that Luzp4 functions as an mRNA export factor in human cells that is able to restore mRNA export function in cells compromised by loss of mRNA export adaptors
We investigated whether Luzp4 RNAi led to a detectable block in mRNA export in Mewo cells using oligo d(T) Fluorescence in situ hybridisation (FISH) (Supplementary Figure S9) and whilst we could see a clear block of export following Alyref RNAi, no such block was seen following Luzp4 RNAi
Summary
The transport of mRNA from the nucleus to the cytoplasm is an essential step in eukaryotic gene expression. It is subject to rigorous quality control to ensure that only fully processed mature mRNA exits the nucleus [1]. A major mRNA export pathway used in human cells involves the multisubunit TREX complex which comprises the THO complex and numerous additional subunits [2,3]. TREX integrates information from transcription [4], splicing [5] and 3 end processing [6,7] to mark mature mRNAs for export. TREX assembly requires Alyref, the THO complex, and is driven by the Uap RNA helicase [3,8]. A number of TREX subunits including Alyref, Chtop and Uif harbour a specific peptide motif (Uap binding motif, UBM) that allows direct interaction with Uap or its paralogue, Ddx39 [9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
