Defining epitranscriptomic hallmarks at the host-parasite interface and their roles in virulence and disease progression in Theileria annulata-infected leukocytes

确定宿主-寄生虫界面处的表观转录组特征及其在泰勒氏锥虫感染的白细胞的毒力和疾病进展中的作用

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Abstract

Theileria parasites are known to induce the transformation of host bovine leukocytes, involved in rapid proliferation, evasion from apoptotic mechanisms, and increased dissemination. In this study, we reveal the involvement of m(6)A RNA modification in T. annulata infection-induced transformation of bovine leukocytes. We conducted m(6)A sequencing and bioinformatics analysis to map the mRNA methylation patterns of T. annulata-infected host leukocytes. We observe specific mRNA modifications for T. annulata-infected leukocytes and a strong correlation between the proliferation rate of the infected Leukocytes with m(6)A modifications We observe that the increased amounts of m(6)A seem to impact some cell cycle dynamics, potentially via modifications of E2F4 mRNA. Moreover, we further identify HIF-1α as a possible driver of these m(6)A RNA modifications that have clear relevance to cellular proliferation dynamics. Overall, our results provide insights into the role of m6A mRNA methylation in the molecular crosstalk between Theileria and their host leukocytes, emphasizing the critical role of mRNA methylation in host-parasite interaction.

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