| First Author | Lee S | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 5791 | PubMed ID | 25557830 |
| Mgi Jnum | J:219752 | Mgi Id | MGI:5629649 |
| Doi | 10.1038/ncomms6791 | Citation | Lee S, et al. (2015) Identification of a subnuclear body involved in sequence-specific cytokine RNA processing. Nat Commun 6:5791 |
| abstractText | Processing of interleukin RNAs must be tightly controlled during the immune response. Here we report that a subnuclear body called the interleukin-6 and -10 splicing activating compartment (InSAC) is a nuclear site of cytokine RNA production and stability. Tat-activating regulatory DNA-binding protein-43 (TDP-43) acts as an InSAC scaffold that selectively associates with IL-6 and IL-10 RNAs in a sequence-specific manner. TDP-43 also recruits key spliceosomal components from Cajal bodies. LPS induces posttranslational modifications of TDP-43; in particular, TDP-43 ubiquitination provides a driving force for InSAC formation. As a consequence, in vivo depletion of TDP-43 leads to a dramatic reduction in the RNA processing and the protein levels of IL-6 in serum. Collectively, our findings highlight the importance of TDP-43-mediated InSAC biogenesis in immune regulation. |
