Lysyl-tRNA synthetase orchestrates translation and hormone signaling during reproduction in Aedes aegypti mosquitoes.

The regulation of mosquito reproduction at the transcriptional level is well understood, but the translational mechanisms remain unclear. Here, we find that lysyl-tRNA synthetase (KARS) is essential for translational regulation and governs mosquito fecundity in a hormone-dependent manner. RNA interference silencing of KARS severely inhibits ovarian maturation and impairs mosquito fecundity. Polysome profiling shows enhanced translation initiation in KARS-deficient mosquitoes, as supported by increased phosphorylation of p70 ribosomal protein S6 kinase and decreased phosphorylation of the translation initiation factor eIF2α. By contrast, incorporated puromycin reveals a reduction in the synthesis of nascent polypeptides such as vitellogenin. Further analysis of ribosome profiling sequencing indicates that the dysregulation of mRNA translation in KARS-deficient mosquitoes was caused by ribosome stalling. Furthermore, the knockdown of KARS results in a significant increase in JH and a decline in 20E, thereby forcing the mosquitoes to maintain prereproductive status and preventing the 20E-activated vitellogenesis. This study demonstrates the function of KARS in regulating reproduction during the gonadotrophic cycle, hence providing insights into the potential control of disease-transmitting mosquitoes.