Seventeen miRNAs encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) have been identified and their functions have begun to be characterized. Among these miRNAs, we report here that miR-K12-7 directly targets the replication and transcription activator (RTA) encoded by open reading frame 50. We found that miR-K12-7 targeted the RTA 3′ untranslated region (RTA3′UTR) in a seed sequence-dependent manner. miR-K12-7-5p derived from miR-K12-7 mediates the inhibition of RTA expression, and the mutation of the seed match site totally abrogated the inhibitory effect of miR-K12-7 on RTA3′UTR. The inhibition of RTA expression by miR-K12-7 was further confirmed in the latently KSHV-infected 293/Bac36 cell line through transient transfection of miR-K12-7 expression plasmid or specific inhibitor of miR-K12-7-5p, respectively. The transient transfection of miR-K12-7 into 293/Bac36 cells reduced RTA expression and the expression of the downstream early genes regulated by RTA, and also the production of progeny virus was significantly reduced after treatment with chemical inducers. Our study revealed that another miRNA, miR-K12-7-5p, targets the viral immediate early gene RTA and that this miRNA contributes to the maintenance of viral latency.
miR-K12-7-5p Encoded by Kaposi's Sarcoma-Associated Herpesvirus Stabilizes the Latent State by Targeting Viral ORF50/RTA
Xianzhi Lin,Deguang Liang,Zhiheng He,Q. Deng,E. Robertson,Ke Lan
Published 2011 in PLoS ONE
ABSTRACT
PUBLICATION RECORD
- Publication year
2011
- Venue
PLoS ONE
- Publication date
2011-01-20
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- 293/bac36 cells
A latently KSHV-infected 293-derived cell line carrying the Bac36 viral genome used for transfection experiments.
Aliases: 293/Bac36
- mir-k12-7
A Kaposi's sarcoma-associated herpesvirus microRNA precursor that produces the mature miR-K12-7-5p strand.
- mir-k12-7-5p
The mature KSHV microRNA strand processed from the miR-K12-7 precursor.
- orf50/rta
The Kaposi's sarcoma-associated herpesvirus replication and transcription activator encoded by open reading frame 50.
Aliases: RTA, ORF50, replication and transcription activator
- rta 3'utr
The 3' untranslated region of the ORF50/RTA transcript used as the miRNA target region in the assay.
Aliases: RTA3'UTR, RTA 3′UTR, ORF50 3'UTR
- viral latency
The latent phase of KSHV infection in which the viral genome is maintained with limited lytic gene expression.
Aliases: latent state
REFERENCES
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