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| Status |
Public on Mar 07, 2017 |
| Title |
Gene Expression Profiling Of TTLL12 Knocked Down Cell With Sendai Virus Treatment |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Upon virus infection, RIG-I-like receptors in host cells recognize viral RNA and activate type I interferon expression. To investigate the role of protein methylation in the anti-viral signaling pathway, we screened all the SET domain containing proteins and identified TTLL12 as a negative regulator of RIG-I signaling pathway. TTLL12 contains SET and TTL domains, which are predicted to have lysine methyltransferase and tubulin tyrosine ligase activities, respectively. Exogenous expression of TTLL12 represses IFN-β expression induced by SeV. TTLL12 deficiency by RNA interference and CRISPR-gRNA techniques increases the induced IFN-β expression and inhibits virus replication in the cell. Gene expression profiling also indicated that TTLL12 specifically inhibits the expression of the downstream genes of innate immunity pathways. Cell fractionation and fluorescent staining indicated that TTLL12 is localized in the cytosol. The study of various mutants suggested TTLL12’s ability to repress RIG-I pathway is probably not dependent on protein modifications. Instead, TTLL12 directly interacts with VISA, TBK1 and IKKε, and inhibits the interactions of VISA with other signaling proteins. Taken together, our findings demonstrate TTLL12 as a negative regulator of RNA-virus-induced type I IFNs expression through inhibition of the interaction of VISA with other proteins.
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| |
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| Overall design |
TTLL12 was knocked down by siRNA in HCT116 and the gene expression profile was studied by RNA sequencing
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| |
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| Contributor(s) |
Ju L, Zhu Y |
| Citation(s) |
28011935 |
| |
| Submission date |
Jun 29, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Pin-Ji Lei |
| E-mail(s) |
leipinji@gmail.com
|
| Organization name |
Massachusetts General Hospital
|
| Department |
Department of Radiation Oncology
|
| Lab |
Edwin L. Steele Laboratories
|
| Street address |
100 Blossom Street
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02114 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA327204 |
| SRA |
SRP077567 |
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