A long noncoding RNA promotes parasite differentiation in African trypanosomes

Fabien Guegan; K. Shanmugha Rajan; Fábio Bento; Daniel Pinto-Neves; Mariana Sequeira; Natalia Gumińska; Seweryn Mroczek; Andrzej Dziembowski; Smadar Cohen-Chalamish; Tirza Doniger; Beathrice Galili; Antonio M. Estévez; Cedric Notredame; Shulamit Michaeli; Luisa M. Figueiredo

doi:10.1126/sciadv.abn2706

A long noncoding RNA promotes parasite differentiation in African trypanosomes

Fabien Guegan, K. Shanmugha Rajan, Fábio Bento, Daniel Pinto-Neves, Mariana Sequeira, Natalia Gumińska, Seweryn Mroczek, Andrzej Dziembowski, Smadar Cohen-Chalamish, Tirza Doniger, Beathrice Galili, Antonio M. Estévez, Cedric Notredame, Shulamit Michaeli, Luisa M. Figueiredo

The Mina and Everard Goodman Faculty of Life Sciences

Bar-Ilan University

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	eabn2706
Journal	Science Advances
Volume	8
Issue number	24
DOIs	https://doi.org/10.1126/sciadv.abn2706
State	Published - 17 Jun 2022

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Guegan, F., Rajan, K. S., Bento, F., Pinto-Neves, D., Sequeira, M., Gumińska, N., Mroczek, S., Dziembowski, A., Cohen-Chalamish, S., Doniger, T., Galili, B., Estévez, A. M., Notredame, C., Michaeli, S., & Figueiredo, L. M. (2022). A long noncoding RNA promotes parasite differentiation in African trypanosomes. Science Advances, 8(24), Article eabn2706. https://doi.org/10.1126/sciadv.abn2706

@article{ad73e7adc4af4ac4af683c1c83745a0e,

title = "A long noncoding RNA promotes parasite differentiation in African trypanosomes",

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.",

author = "Fabien Guegan and Rajan, {K. Shanmugha} and F{\'a}bio Bento and Daniel Pinto-Neves and Mariana Sequeira and Natalia Gumi{\'n}ska and Seweryn Mroczek and Andrzej Dziembowski and Smadar Cohen-Chalamish and Tirza Doniger and Beathrice Galili and Est{\'e}vez, {Antonio M.} and Cedric Notredame and Shulamit Michaeli and Figueiredo, {Luisa M.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved",

year = "2022",

month = jun,

day = "17",

doi = "10.1126/sciadv.abn2706",

language = "الإنجليزيّة",

volume = "8",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "24",

}

Guegan, F, Rajan, KS, Bento, F, Pinto-Neves, D, Sequeira, M, Gumińska, N, Mroczek, S, Dziembowski, A, Cohen-Chalamish, S, Doniger, T, Galili, B, Estévez, AM, Notredame, C, Michaeli, S & Figueiredo, LM 2022, 'A long noncoding RNA promotes parasite differentiation in African trypanosomes', Science Advances, vol. 8, no. 24, eabn2706. https://doi.org/10.1126/sciadv.abn2706

TY - JOUR

T1 - A long noncoding RNA promotes parasite differentiation in African trypanosomes

AU - Guegan, Fabien

AU - Rajan, K. Shanmugha

AU - Bento, Fábio

AU - Pinto-Neves, Daniel

AU - Sequeira, Mariana

AU - Gumińska, Natalia

AU - Mroczek, Seweryn

AU - Dziembowski, Andrzej

AU - Cohen-Chalamish, Smadar

AU - Doniger, Tirza

AU - Galili, Beathrice

AU - Estévez, Antonio M.

AU - Notredame, Cedric

AU - Michaeli, Shulamit

AU - Figueiredo, Luisa M.

PY - 2022/6/17

Y1 - 2022/6/17

N2 - 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.

AB - 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.

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U2 - 10.1126/sciadv.abn2706

DO - 10.1126/sciadv.abn2706

M3 - مقالة

C2 - 35704590

SN - 2375-2548

VL - 8

JO - Science Advances

JF - Science Advances

IS - 24

M1 - eabn2706

ER -

A long noncoding RNA promotes parasite differentiation in African trypanosomes

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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