Λεπτομέρειες βιβλιογραφικής εγγραφής
| Τίτλος: |
A TCER-1-siRNA regulatory axis suppresses antibacterial innate immunity in C. elegans. |
| Συγγραφείς: |
Naim, Nikki, Amrit, Francis R.G., Devare, Mayur N., Osman, Guled A., Bahr, Laura L., Henry, Hannah, Montgomery, Brooke E., Kuhn, Spencer M., Montgomery, Taiowa A., Ghazi, Arjumand |
| Πηγή: |
PLoS Pathogens; 7/28/2026, Vol. 22 Issue 7, p1-14, 14p |
| Θεματικοί όροι: |
Small interfering RNA, Caenorhabditis elegans, Natural immunity |
| Περίληψη: |
Small interfering RNAs (siRNAs) are important regulators of gene expression with well-established roles in pathogen defense. Yet, their specific roles in antibacterial immunity are not well understood. Here, we identify an siRNA pathway involved in repressing antibacterial innate immunity in Caenorhabditis elegans. We show that genes required for the biogenesis or function of WAGO Argonaute-associated siRNAs, called 22G-RNAs, function in a common genetic pathway with the immune-suppressive transcription elongation and splicing factor TCER-1 to inhibit immunity. Loss of tcer-1 led to reduced levels of 22G-RNAs from a subset of WAGO targets, while mutations in several WAGO 22G-RNA pathway genes phenocopied the enhanced immunoresistance of tcer-1 mutants, suggesting a shared regulatory module. Integrative 22G-RNA-mRNA analyses and molecular genetic studies show that this module does not induce widespread gene silencing, but instead targets a restricted set of immune-relevant effectors, including scrm-4, which encodes a conserved phospholipid translocase that promotes host resistance. Together, our findings establish endogenous WAGO 22G-RNAs as repressors of antibacterial immunity and identify TCER-1 as a physiological regulator that promotes 22G-RNA biogenesis to constrain host defense. The results uncover a previously unrecognized small RNA-dependent mechanism linking transcription, metabolism, and antibacterial innate immunity. Author summary: Small interfering RNAs (siRNAs) are recognized as having critical roles in controlling how genes and proteins involved in diverse biological processes are expressed, including during immune response following viral infections. But, their role in immunity against bacterial pathogens is not clear. We provide evidence for an siRNA pathway, regulated by the C. elegans protein TCER-1, that represses antibacterial innate immunity. TCER-1, along with WAGO Argonaute proteins involved in 22G-RNA biogenesis, promotes the production of a subset of 22G-RNAs that repress a select group of targets, including a lipid-modifying scramblase enzyme, SCRM-4, that is necessary for immune activation. This results reveals a novel small RNA-dependent mechanism of antibacterial innate immunity. [ABSTRACT FROM AUTHOR] |
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| Βάση Δεδομένων: |
Complementary Index |