Abstract
The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs.
Highlights
Post-transcriptional events which regulate mRNA biogenesis are fundamental to the control of gene expression [1]
Due to the reliance of herpesviruses on the host cell machinery for efficient processing of their mRNAs, an immediate issue arises concerning the mechanism by which the viral intronless mRNAs are efficiently exported from the nucleus, given that the majority of cellular bulk mRNA nuclear export is intimately linked, and dependent upon, splicing [29]. We have investigated this potential roadblock to herpesvirus gene expression and replication in the gamma-2 herpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV) [30], which is associated with the AIDS-related malignancies Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman’s disease [31,32,33]
To determine whether ORF57 interacts with alternative export adaptor proteins, GST-pulldown and coimmunoprecipitations assays were performed to assess if ORF57 interacted with the recently identified UAP56 interacting protein, UAP56-interacting factor (UIF)
Summary
Post-transcriptional events which regulate mRNA biogenesis are fundamental to the control of gene expression [1]. A nascent mRNA is steered through multimeric RNA-protein complexes that mediate its capping, splicing, polyadenylation, nuclear export and its translation [2,3]. The act of splicing is coupled to the deposition of two distinct multiple protein complexes onto the mRNA which are involved in further processing events, namely the human transcription and export complex (hTREX) [5,6,7] and the exonexon junction complex (EJC) [8]. The hTREX complex associates with the 59end of the first exon by virtue of interactions with the cap-binding complex, and facilitates the nuclear export of the bulk mRNA through the TAP-mediated pathway [6]. The EJC is deposited 20–24 nucleotides upstream of each exon-exon boundary and plays a role in mRNA surveillance [9] and translation enhancement [10,11,12]
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.
