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影响因子：11.205

DOI码：10.1073/pnas.2110713119

发表刊物：Proc Natl Acad Sci USA

关键字：RNA bisulfite sequencing; RNA methyltransferase; epitranscriptomic modifications; gametocytogenesis; gene knockout

摘要：5-methylcytosine (m5C) is an important epitranscriptomic modifica-tion involved in messenger RNA (mRNA) stability and translationefficiency in various biological processes. However, it remainsunclear if m5Cmodification contributes to the dynamic regulationof the transcriptome during the developmental cycles ofPlasmo-diumparasites. Here, we characterize the landscape of m5CmRNAmodifications at single nucleotide resolution in the asexual replica-tion stages and gametocyte sexual stages of rodent (Plasmodiumyoelii) and human (Plasmodium falciparum) malaria parasites.While different representations of m5C-modified mRNAs are asso-ciated with the different stages, the abundance of the m5Cmarkeris strikingly enhanced in the transcriptomes of gametocytes. Ourresults show that m5Cmodifications confer stability to thePlasmo-diumtranscripts and that aPlasmodiumortholog of NSUN2 is amajor mRNA m5C methyltransferase in malaria parasites. Uponknockout ofP. yoelii nsun2(pynsun2), marked reductions of m5Cmodification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impairedgametocyte production in the knockout rodent malaria parasites.Restoration of thensun2gene in the knockout parasites rescuedthe gametocyte production phenotype as well as m5Cmodificationof the gametocytogenesis-associated transcripts. Together withthe mRNA m5Cprofiles for two species ofPlasmodium,ourfind-ings demonstrate a major role for NSUN2-mediated m5Cmodifica-tions in mRNA transcript stability and sexual differentiation inmalaria parasites.

论文类型：期刊论文

学科门类：医学

一级学科：基础医学

卷号：119

期号：9

页面范围：e2110713119

是否译文：否

收录刊物：SCI

发布期刊链接：https://doi.org/10.1073/pnas.2110713