SFB 1054 Seminar - Osamu Takeuchi

Title: Regulation of immune responses by RNA binding proteins

Activation of immune cells leads to the induction of a set of immune-related genes. In the innate immune system, sensing of pathogens by Toll-like receptors (TLRs) induces proinflammatory cytokine genes. The expression of proinflammatory cytokines is controlled at the transcriptional and posttranscriptional levels. Posttranscriptional control of cytokine mRNAs is critical for preventing excess and persistent production of cytokines by degrading them via a set of RNA binding proteins (RBPs) recognizing cis-elements present in the mRNA 3’-untranslated region. Among RBPs, Roquin recognizes stem-loop structures present in mRNAs encoding inflammatory proteins and degrades them by recruiting RNases. We identified Regnase-1 (also known as MCPIP1) as an endoribonuclease essential for the degradation of immune-related mRNAs such as Il6 induced by TLR stimuli in innate immune cells. Regnase-1 is also critical for suppressing T cell activation and maintenance of immune homeostasis in mice. We found that Regnase-1 and Roquin regulate an overlapping set of mRNAs via common stem-loop structures. However, Regnase-1 and Roquin function in distinct subcellular locations in distinct molecular mechanisms. Specifically, Regnase-1 specifically degrades translationally active mRNAs depending on UPF1, a helicase essential for the nonsense-mediated mRNA decay (NMD). Regnase-1-mediated mRNA decay is triggered by the phosphorylation of UPF1 by a kinase SMG1, which can be modified by its inhibitor. Taken together, our findings reveal that differential regulation of immune-related mRNAs by two RNA binding proteins, Regnase-1 and Roquin, depends on their translation status and enables elaborate control of inflammation. We further tried to identify novel RNA binding proteins suppressing virus infection by using HIV-1 as the model. I will also describe identification of a novel RNA binding protein involved in degradation of viral RNAs.

Osamu Takeuchi - Website

Venue:

BioMedical Center (BMC), Room N 01.017,
Großhaderner Str. 9, Planegg-Martinsried

Host: Dirk Baumjohann (B12)