Majerciak, V., Yamanegi, K., Allemand, E., Kruhlak, M., Krainer, A. R., Zheng, Z. M. (March 2008) Kaposi sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes the expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing. J Virol, 82 (6). pp. 2792-2801.
Abstract
KSHV ORF57 facilitates the expression of both intronless viral ORF59 genes and intron-containing viral K8 and K8.1 genes (Majerciak, V., N. Pripuzova, J. P. McCoy, S. J. Gao, and Z. M. Zheng. 2007. J.Virol. 81:1062-1071). In this report, we showed that disruption of ORF57 in a KSHV genome led to increased accumulation of ORF50 and K8 pre-mRNAs and reduced expression of ORF50 and K-bZIP proteins, but had no effect on LANA. Cotransfection of ORF57 and K8* cDNA which retains a suboptimal intron of K8 pre-mRNA due to alternative splicing promoted RNA splicing of K8* and production of K8* (K-bZIP). Although EBV EB2, a closely related homolog of ORF57, had a similar activity in the cotransfection assays, HSV-1 ICP27 was inactive. This enhancement of RNA splicing by ORF57 correlates with the intact N-terminal NLS motifs of ORF57 and takes place in the absence of other viral proteins. In activated KSHV(+) B cells, KSHV ORF57 partially co-localizes with splicing factors in nuclear speckles and assembles into spliceosomal complexes in association with low-abundance viral ORF50 and K8 pre-mRNAs and essential splicing components. The association of ORF57 with snRNAs occurs by ORF57-Sm protein interaction. We also found that ORF57 binds K8* pre-mRNAs in vitro in the presence of nuclear extracts. Collectively our data indicate that KSHV ORF57 functions as a novel splicing factor in the spliceosome-mediated splicing of viral RNA transcripts.
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