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A long noncoding RNA promotes parasite differentiation in African trypanosomes
Science Advances ( IF 13.6 ) Pub Date : 2022-06-15 , DOI: 10.1126/sciadv.abn2706
Fabien Guegan 1 , K Shanmugha Rajan 2 , Fábio Bento 1 , Daniel Pinto-Neves 1 , Mariana Sequeira 1 , Natalia Gumińska 3 , Seweryn Mroczek 3, 4 , Andrzej Dziembowski 3 , Smadar Cohen-Chalamish 2 , Tirza Doniger 2 , Beathrice Galili 2 , Antonio M Estévez 5 , Cedric Notredame 6, 7 , Shulamit Michaeli 2 , Luisa M Figueiredo 1
Affiliation  

The parasite Trypanosoma brucei causes African sleeping sickness that is fatal to patients if untreated. Parasite differentiation from a replicative slender form into a quiescent stumpy form promotes host survival and parasite transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation in other eukaryotes. To determine whether lncRNAs are also involved in parasite differentiation, we used RNA sequencing to survey the T. brucei genome, identifying 1428 previously uncharacterized lncRNA genes. We find that grumpy lncRNA is a key regulator that promotes parasite differentiation into the quiescent stumpy form. This function is promoted by a small nucleolar RNA encoded within the grumpy lncRNA. snoGRUMPY binds to messenger RNAs of at least two stumpy regulatory genes, promoting their expression. grumpy overexpression reduces parasitemia in infected mice. Our analyses suggest that T. brucei lncRNAs modulate parasite-host interactions and provide a mechanism by which grumpy regulates cell differentiation in trypanosomes.

中文翻译:

一种长的非编码 RNA 促进非洲锥虫的寄生虫分化

寄生虫布氏锥虫导致非洲昏睡病,如果不治疗,对患者来说是致命的。寄生虫从复制的细长形式分化为静止的矮胖形式可促进宿主存活和寄生虫传播。已知长链非编码 RNA (lncRNA) 可调节其他真核生物的细胞分化。为了确定 lncRNA 是否也参与寄生虫分化,我们使用 RNA 测序来调查T. brucei基因组,鉴定了 1428 个以前未鉴定的 lncRNA 基因。我们发现脾气暴躁lncRNA 是促进寄生虫分化为静止的短节形式的关键调节因子。这个功能是由一个小核仁 RNA 编码的脾气暴躁lncRNA。斯诺格鲁比与至少两个短调控基因的信使 RNA 结合,促进它们的表达。脾气暴躁过表达可减少受感染小鼠的寄生虫血症。我们的分析表明T. bruceilncRNA 调节寄生虫与宿主的相互作用并提供一种机制脾气暴躁调节锥虫中的细胞分化。
更新日期:2022-06-15
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