Kaposi's sarcoma-associated herpesvirus ORF57 protein: exploiting all stages of viral mRNA processing

Abstract

Nuclear mRNA export is a highly complex and regulated process in cells. Cellular transcripts must undergo successful maturation processes, including splicing, 5'-, and 3'-end processing, which are essential for assembly of an export competent ribonucleoprotein particle. Many viruses replicate in the nucleus of the host cell and require cellular mRNA export factors to efficiently export viral transcripts. However, some viral mRNAs undergo aberrant mRNA processing, thus prompting the viruses to express their own specific mRNA export proteins to facilitate efficient export of viral transcripts and allowing translation in the cytoplasm. This review will focus on the Kaposi's sarcoma-associated herpesvirus ORF57 protein, a multifunctional protein involved in all stages of viral mRNA processing and that is essential for virus replication. Using the example of ORF57, we will describe cellular bulk mRNA export pathways and highlight their distinct features, before exploring how the virus has evolved to exploit these mechanisms.

Figure 1

Formation of transcription-coupled export (TREX) on the 5'-end of the mRNA through direct interactions with the cap-binding complex (yellow).

Figure 2

UAP56 assembles the TREX complex in an ATP-dependent manner.

Figure 3

Binding of Nxf1/TAP to Aly and Thoc5 induces a conformational change in the protein which allows RNA binding [60] and leads to the release of UAP56.

Figure 4

Handover of mRNA from TREX onto Nxf1/TAP and translocation through the nuclear pore complex (NPC).

Figure 5

Open reading frame (ORF) 57 recruits the TREX complex onto viral mRNA, relocalises to the nucleolus and leaves the nucleus through the NPCs.

Figure 6

ORF57 interacts directly with PYM to enhance translation.