Epstein-Barr virus BHRF1 micro- and stable RNAs during latency III and after induction of replication.
Epstein-Barr virus (EBV) microRNAs miR-BHRF1-1, -2, and -3 have been detected in latency III-infected lymphoblasts, where they are encoded within EBNA transcripts (X. Cai, A. Schafer, S. Lu, J. P. Bilello, R. C. Desrosiers, R. Edwards, N. Raab-Traub, and B. R. Cullen, PLoS Pathog. 2:e23, 2006). In latency III-infected lymphoblasts, we have also identified a stable 1.3-kb RNA, which begins 3' to miR-BHRF1-1, includes the BHRF1 open reading frame, and ends near miR-BHRF1-2. This 1.3-kb RNA is the residue of Drosha cleavage of the BHRF1 microRNAs from EBNA transcripts. Early after induction of EBV replication in latency I-infected Akata lymphoblasts, BHRF1 spliced 1.4-kb mRNA accumulated along with low levels of miR-BHRF1-2 and -3 and a 0.9-kb Drosha or miR-BHRF1-2 cleavage product of BHRF1 mRNA. The turning on of latency III infection at 48 to 72 h after induction of EBV replication was associated with higher miR-BHRF1-1, -2, and -3 levels; accumulation of the 1.3-kb RNA residue in the nucleus; abundant BHRF1 spliced 1.4-kb mRNA in the cytoplasm; and more abundant 0.9-kb mRNA cleavage product in the cytoplasm. These findings implicate miR-BHRF1-2 in 3' cleavage of BHRF1 mRNA in the cytoplasm and Drosha in cleavage of latency III EBNA and EBV replication-associated BHRF1 transcripts in the nucleus.
Xing
Li
L
Brigham and Women's Hospital, Harvard Medical School, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115-5804, USA.
Kieff
Elliott
E
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000502:physiology; D012326:RNA Splicing / Q000502:physiology; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*; D017735:Virus Latency / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
C083278:BHRF1 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; C517918:DROSHA protein, human; D043244:Ribonuclease III