Regulation of Viral mRNA Export from the Nucleus
Peter Lischka and Thomas Stamminger
from: Cytomegaloviruses: Molecular Biology and Immunology (Edited by: Matthias J. Reddehase). Caister Academic Press, U.K. (2006)
Abstract
Nuclear export of mRNA is a central step in eukaryotic gene expression. Thus, viruses that replicate within the nucleus have evolved regulatory proteins that are believed to up-regulate replication by facilitating the selective nuclear export of viral mRNA transcripts. Complex retroviruses such as human immunodeficiency virus type 1 encode sequence-specific RNA binding proteins that recruit the cellular nuclear export receptor CRM1 to incompletely spliced viral mRNAs. In contrast, herpesviruses encode nucleocytoplasmic shuttling proteins that direct their intronless mRNAs to the cellular mRNA export pathway whose key components are the heterodimeric mRNA export receptor TAP-p15, the adapter protein REF and the DEAD-box RNA helicase UAP56. Although these viral shuttling proteins are conserved among all herpesviruses, it appears that individual members have shared and separate features. Thus, these proteins share the ability (1) to shuttle between the nucleus and the cytoplasm (2) to bind RNA and (3) to export RNAs from the nucleus. In other aspects, these viral shuttling proteins are different. Whereas the HSV-1 mRNA export factor ICP27 and its EBV counterpart EB2 facilitate RNA export by accessing the TAP pathway via direct protein interaction with REF, the HCMV UL69 protein targets this pathway by binding to the RNA helicase UAP56 that acts upstream of REF. In addition, a functional interaction between pUL69 and the transcription elongation factor hSPT6 was described. Since UAP56 also affects transcription elongation, we hypothesize that pUL69, by interacting with both hSPT6 and UAP56, is a factor which optimizes the coupling of transcription elongation to mRNA export during viral replication read more ...
