A long noncoding RNA promotes parasite differentiation in African trypanosomes-Reference-Cited by-同舟云学术

A long noncoding RNA promotes parasite differentiation in African trypanosomes

Published:2022-06-17 Issue:24 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Guegan Fabien¹^ORCID,Rajan K. Shanmugha²^ORCID,Bento Fábio¹^ORCID,Pinto-Neves Daniel¹,Sequeira Mariana¹^ORCID,Gumińska Natalia³^ORCID,Mroczek Seweryn³⁴^ORCID,Dziembowski Andrzej³^ORCID,Cohen-Chalamish Smadar²,Doniger Tirza²^ORCID,Galili Beathrice²,Estévez Antonio M.⁵^ORCID,Notredame Cedric⁶⁷^ORCID,Michaeli Shulamit²^ORCID,Figueiredo Luisa M.¹^ORCID

Affiliation:

1. Instituto de Medicina Molecular–Joao Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

2. The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.

3. Laboratory of RNA Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.

4. Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Warsaw, Poland.

5. Instituto de Parasitologia y Biomedicina ‘Lopez-Neyra,’ IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento 17, 18016 Armilla, Granada, Spain.

6. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.

7. Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference74 articles.

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