The human cytomegalovirus regulatory protein UL69 and its effect on mRNA export

Abstract

One of the characteristic features of herpesviruses is that most of their genes are intronless. Thus, their replication relies on the selective nuclear export of intronless viral mRNAs, which have to compete with the nuclear export of bulk spliced cellular mRNAs. Therefore, the regulation of nuclear mRNA export is crucial for the replication and pathogenesis of herpesviruses. Besides the thymidine kinase transcript of herpes simplex virus type 1, which contains specific sequences to facilitate the nuclear export of intronless mRNA, other cis-acting RNA elements for nuclear mRNA export have not yet been identified in the rest of herpesviral intronless mRNAs. Instead, emerging studies show that herpesviruses encode viral mRNA export factors, which interact with components of the major cellular mRNA export pathway, the RNA polymerase II transcription complex and specific splicing factors to selectively export intronless herpesviral mRNAs to the cytoplasm in infected cells. These herpesviral mRNA export factors are members of a conserved gene family that can be found in all herpesviruses. The human cytomegalovirus transactivator protein UL69, which has been demonstrated to belong to this conserved protein family, shares common features with its herpesviral homologues but also possesses unique properties that will be discussed in this review.