A role for H/ACA and C/D small nucleolar RNAs in viral replication.
We have employed gene-trap insertional mutagenesis to identify candidate genes whose disruption confer phenotypic resistance to lytic infection, in independent studies using 12 distinct viruses and several different cell lines. Analysis of >2,000 virus-resistant clones revealed >1,000 candidate host genes, approximately 20 % of which were disrupted in clones surviving separate infections with 2-6 viruses. Interestingly, there were 83 instances in which the insertional mutagenesis vector disrupted transcripts encoding H/ACA-class and C/D-class small nucleolar RNAs (SNORAs and SNORDs, respectively). Of these, 79 SNORAs and SNORDs reside within introns of 29 genes (predominantly protein-coding), while 4 appear to be independent transcription units. siRNA studies targeting candidate SNORA/Ds provided independent confirmation of their roles in infection when tested against cowpox virus, Dengue Fever virus, influenza A virus, human rhinovirus 16, herpes simplex virus 2, or respiratory syncytial virus. Significantly, eight of the nine SNORA/Ds targeted with siRNAs enhanced cellular resistance to multiple viruses suggesting widespread involvement of SNORA/Ds in virus-host interactions and/or virus-induced cell death.
Zirus, Inc., 1384 Buford Business Boulevard, Suite 700, Buford, GA, 30518, USA, jmurray100@yahoo.com.
James L
JL
Murray
Jinsong
J
Sheng
Donald H
DH
Rubin
D002460:Cell Line; D006801:Humans; D016254:Mutagenesis, Insertional; D034741:RNA, Small Interfering / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
D034741:RNA, Small Interfering; D020537:RNA, Small Nucleolar