Fig. 8. Schematic diagram: TUT1-mediated alternative splicing produces a truncated protein NCOR2-013 that suppresses T. marneffei-stimulated macrophage inflammation.

T. marneffei infection of macrophages promoted AS of NCOR2, in which TUT1 is an AS regulator, and NCOR2-013, a truncated protein of NCOR2/SMRT, was significantly upregulated after T. marneffei infection. Mechanistic analysis reveals that NCOR2-013 forms a co-inhibitory complex with TBL1XR1/TBLR1 and HDAC3. Consequently, this complex inhibits the JunB-mediated transcriptional activation of pro-inflammatory cytokines by suppressing histone acetylation, thereby regulating the expression of inflammatory factors such as IL-1β and TNF-α.