Evolutionary insights and poly(I:C)-induced changes in expression and m⁶A modifications of il17ra and il17rc in...

Interleukin-17 receptor A (IL17RA) and IL17RC form a receptor complex critical for initiating IL-17A-mediated immune responses, a hallmark of T helper 17 (Th17) cells. In this study, il17ra and il17rc were identified in miiuy croaker (Miichthys miiuy) and bioinformatics analysis revealed their evolutionary and structural conservation, underscoring their roles in immunity. However, there has been little research on the IL-17 receptor family from the perspective of N6-methyladenosine (m⁶A) modifications. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq), we identified strong m⁶A modifications on the last exons of il17ra and il17rc, validated by MeRIP-PCR. Poly(I:C) stimulation significantly upregulated il17ra and il17rc expression, while reducing their m⁶A modification levels, implicating these changes in antiviral immunity. Interestingly, cycloleucine (CL), a well-known methylation inhibitor, did not alter the expression of il17ra and il17rc but promoted the nuclear-to-cytoplasmic transport of il17ra mRNA, potentially influencing its translation process. These findings provide valuable insights into the regulatory roles of m⁶A modifications in il17ra and il17rc function and highlight their importance in the antiviral immune response.