Priming of influenza mRNA transcription is inhibited in CHO cells treated with the methylation inhibitor, neplanocin A.
Chinese hamster ovary cells were pretreated with Neplanocin A, a potent inhibitor of RNA methylation. Analysis of polyadenylated RNA from treated cells by high-pressure liquid chromatography revealed marked decreases of 2'-O-methylation within mRNA cap structures and of internal N6-methyladenosine residues. In these Neplanocin A-treated cells, influenza viral mRNA accumulation was virtually abolished. Cellular RNA from Neplanocin A-treated cells was substantially less efficient than RNA from control cells in priming cell-free influenza transcription reactions. These results suggest that the observed inhibition of influenza virus replication is due at least in part to impaired recognition of undermethylated cellular mRNA cap structures by the influenza polymerase complex.
Ransohoff
R M
RM
Department of Neurology, Cleveland Clinic Foundation, OH.
Narayan
P
P
Ayers
D F
DF
Rottman
F M
FM
Nilsen
T W
TW
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D008745:Methylation; D009693:Nucleic Acid Hybridization; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000235:genetics; D012315:RNA Caps / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014764:Viral Proteins / Q000096:biosynthesis
D000998:Antiviral Agents; D012315:RNA Caps; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; C031096:neplanocin A; D000241:Adenosine