A posttranscriptional regulator of Kaposi's sarcoma-associated herpesvirus interacts with RNA-binding protein PCBP1 and controls gene expression through the IRES.
Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8, HHV-8) belongs to the gamma-herpesvirus subfamily. The KSHV ORF57 gene is thought to be a homolog of posttranscriptional regulators that are conserved in the herpesvirus family and are essential for replication. We generated specific monoclonal antibodies (mAbs) against the ORF57 protein that detected the 51-kDa protein expressed in the nucleus of KSHV-infected cells. We also found that the ORF57 protein interacted with poly(rC)-binding protein 1 (PCBP1), a cellular RNA-binding, posttranscriptional regulator. ORF57's interaction with PCBP1 enhanced the activity of not only poliovirus internal ribosome-entry site (IRES)-dependent translation but also X-linked inhibitor of apoptosis (XIAP) and KSHV vFLIP IRES. Actually, when ORF57 expression was induced by the expression of replication and transcription activator (RTA) in KSHV-infected cells, the expression of XIAP was enhanced. These results suggest that ORF57 binds to PCBP1 as a functional partner for posttranscriptional regulation and is involved in the regulation of the expression of both cellular and viral genes through IRESs.
Nishimura
Ken
K
Department of Microbiology, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
Ueda
Keiji
K
Guwanan
Edhi
E
Sakakibara
Shuhei
S
Do
Eunju
E
Osaki
Eriko
E
Yada
Kaori
K
Okuno
Toshiomi
T
Yamanishi
Koichi
K
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000502:physiology*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D010449:Peptide Mapping; D012323:RNA Processing, Post-Transcriptional; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D014764:Viral Proteins / Q000502:physiology
D018076:DNA, Complementary; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C094604:PCBP1 protein, human; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014764:Viral Proteins