Post-transcriptional mechanisms of deregulation of MYC following conversion of a human B cell line by Epstein-Barr virus.
By utilizing an Epstein-Barr virus (EBV)-negative Burkitt's lymphoma line (BJAB) and several EBV-positive sub-lines derived from it by in vitro infection, it has been shown previously that the presence of the EBV genome in this B cell line is reversibly associated with deregulation of MYC expression. Specifically, the decline in the level of MYC transcripts observed in the EBV-negative BJAB line as cells approach stationary phase of growth is abrogated in the presence of the virus. In the studies described herein, the mechanism of deregulation of MYC in EBV-converted BJAB cells was examined. It was shown that the presence of EBV in BJAB cells was not associated with changes in the rate of transcription from exons I, II or III of MYC as cells approached stationary phase of growth. In contrast, the stability of MYC mRNA was altered in EBV-positive BJAB cells. Specifically, the half-life of MYC mRNA increased from less than 36 to greater than 70 min in EBV-positive BJAB lines as cells progressed from early to late exponential phase of growth. This alteration in stability of MYC transcripts was reversibly associated with the presence of the virus, since an EBV-negative revertant BJAB line did not display an increase in stability of MYC transcripts in late exponential phase of growth. In addition, progression from early to late exponential phase of growth in two EBV-immortalized lymphoblastoid lines derived from normal human B cells was also associated with prolongation of the half-life of MYC.(ABSTRACT TRUNCATED AT 250 WORDS)
Lacy
J
J
Department of Medicine, Yale University School of Medicine, New Haven, CT 06510.
Summers
W P
WP
Summers
W C
WC
D001402:B-Lymphocytes; D002051:Burkitt Lymphoma; D002460:Cell Line; D002472:Cell Transformation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015183:Restriction Mapping; D014158:Transcription, Genetic
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger