LNCGM1082-mediated NLRC4 activation drives resistance to bacterial infection

The activation of NLRC4 is a major host response against intracellular bacteria infection.However,NLRC4 activation after a host senses diverse stimuli is difficult to understand.Here,we found that the IncRNA LNCGM1082 plays a critical role in the activation of NLRC4.LNCGM1082 in macrophages affects the maturation of interleukin(IL)-1βand pyroptotic cell death only after exposure to an NLRC4 ligand.Similar to NLRC4-/-mice,LNCGM1082-/-mice were highly sensitive to Salmonella Typhimurium(S.T)infection.LNCGM1082 deficiency in mouse or human macrophages inhibited IL-1βmaturation and pyroptosis.Mechanistically,LNCGM1082 induced the binding of PKCS with NLRC4 in both mice and humans.In contrast,NLRC4 did not bind PKCo in LNCGM1082-/-macrophages.The activity of the IncRNA LNCGM1082 induced by S.T may be mediated through TLR5 in the macrophages of both mice and humans.In summary,our data indicate that TLR5-mediated LNCGM1082 activity can promote the binding of PKC with NLRC4 to activate NLRC4 and induce resistance to bacterial infection.

Seryl tRNA synthetase cooperates with POT1 to regulate telomere length and cellular senescence

Deregulated telomere length is a causative factor in many physiological and pathological processes,including aging and cancer.Many studies focusing on telomeres have revealed important roles for cooperation between the Shelterin protein complex and telomerase in maintaining telomere length.However,it remains largely unknown whether and how aging-related stresses,such as deregulated protein homeostasis,impact telomere length.Here,we explored the possible roles of aminoacyl tRNA synthetases(AARSs),key enzymes catalyzing the first reactions in protein synthesis,in regulating telomere length and aging.We selected seryl tRNA synthetase(SerRS)since our previous studies discovered expanded functions of SerRS in the nucleus in addition to its canonical cytoplasmic role in protein synthesis.In this study,we revealed that overexpression of SerRS promoted cellular senescence and inhibited the growth of cervical tumor xenografts in mice by triggering the senescence of tumor cells.In the nucleus,SerRS directly bound to telomeric DNA repeats and tethered more POT1 proteins to telomeres through a direct interaction between the UNE-S domain of SerRS and the OB1 domain of POT1.We further demonstrated that SerRS-induced enrichment of POT1 prevented the recruitment of telomerase to telomeres,resulting in progressive telomere shortening.Our data suggested a possible molecular link between protein synthesis and telomere length control,the deregulation of which may be associated with aging and cancer.