Guegan Fabien, Rajan K Shanmugha, Bento Fábio, Pinto-Neves Daniel, Sequeira Mariana, Gumińska Natalia, Mroczek Seweryn, Dziembowski Andrzej, Cohen-Chalamish Smadar, Doniger Tirza, Galili Beathrice, Estévez Antonio M, Notredame Cedric, Michaeli Shulamit, Figueiredo Luisa M
Instituto de Medicina Molecular-Joao Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.
Sci Adv. 2022 Jun 17;8(24):eabn2706. doi: 10.1126/sciadv.abn2706. Epub 2022 Jun 15.
The parasite 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 genome, identifying 1428 previously uncharacterized lncRNA genes. We find that 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 lncRNA. binds to messenger RNAs of at least two stumpy regulatory genes, promoting their expression. overexpression reduces parasitemia in infected mice. Our analyses suggest that lncRNAs modulate parasite-host interactions and provide a mechanism by which regulates cell differentiation in trypanosomes.
这种寄生虫会引发非洲昏睡病，若不治疗，对患者来说是致命的。寄生虫从增殖性的细长形态分化为静止的粗短形态，这有利于宿主存活和寄生虫传播。已知长链非编码RNA（lncRNAs）在其他真核生物中调节细胞分化。为了确定lncRNAs是否也参与寄生虫分化，我们使用RNA测序对基因组进行了检测，鉴定出1428个以前未被表征的lncRNA基因。我们发现lncRNA是促进寄生虫分化为静止粗短形态的关键调节因子。这种功能是由lncRNA中编码的一种小核仁RNA促进的。它与至少两个粗短形态调节基因的信使RNA结合，促进它们的表达。其过表达可降低感染小鼠的寄生虫血症。我们的分析表明，lncRNAs调节寄生虫与宿主的相互作用，并提供了一种机制，通过这种机制来调节锥虫中的细胞分化。
