A long non-coding RNA controls parasite differentiation in African trypanosomes

Trypanosoma brucei causes African sleeping sickness, a fatal human disease. Its differentiation from replicative slender form into quiescent stumpy form promotes host survival and parasite transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation. To determine whether lncRNAs are involved in parasite differentiation we used RNAseq to survey the T. brucei lncRNA gene repertoire, identifying 1,428 previously uncharacterized lncRNA genes. We analysed grumpy, a lncRNA located immediately upstream of an RNA-binding protein that is a key differentiation regulator. Grumpy over-expression resulted in premature parasite differentiation into the quiescent stumpy form, and subsequent impairment of in vivo infection, decreasing parasite load in the mammalian host, and increasing host survival. Our analyses suggest Grumpy is one of many lncRNA that modulate parasite-host interactions, and lncRNA roles in cell differentiation are probably commonplace in T. brucei.

布氏锥虫（Trypanosoma brucei）可引发非洲昏睡病——一种致死性人类疾病。该寄生虫可从可增殖的细长形态分化为静息的粗短形态，这一过程有助于宿主存活与寄生虫的传播。已知长链非编码RNA（lncRNAs）能够调控细胞分化过程。为探究长链非编码RNA是否参与该寄生虫的分化过程，我们通过RNAseq分析了布氏锥虫的长链非编码RNA基因库，鉴定出1428个此前未被表征的长链非编码RNA基因。我们对grumpy这一长链非编码RNA开展了分析：该RNA紧邻作为关键分化调控因子的RNA结合蛋白的上游区域。过表达grumpy可导致寄生虫提前分化为静息的粗短形态，并损害其体内感染能力，具体表现为降低哺乳动物宿主内的寄生虫载量，同时延长宿主存活时间。我们的分析表明，grumpy是调控寄生虫-宿主互作的众多长链非编码RNA之一，而长链非编码RNA在布氏锥虫细胞分化中的作用可能普遍存在。