Expression of the RNA-binding protein RBP10 promotes the bloodstream-form differentiation state in Trypanosoma brucei

PLoS Pathogens

Elisha Mugo¹  Christine Clayton¹ 

[1] DKFZ-ZMBH Alliance, Zentrum für Molekulare Biologie der Universität Heidelberg, University of Heidelberg, Heidelberg, Germany

关键词: Trypanosoma;    Messenger RNA;    RNA interference;    Cell differentiation;    Sequence motif analysis;    RNA-binding proteins;    Epimastigotes;    Protein translation;   

DOI  :  10.1371/journal.ppat.1006560

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

In nearly all eukaryotes, cellular differentiation is governed by changes in transcription, and stabilized by chromatin and DNA modification. Gene expression control in the pathogen Trypanosoma brucei, in contrast, relies almost exclusively on post-transcriptional mechanisms, so RNA binding proteins must assume the burden that is usually borne by transcription factors. T. brucei multiply in the blood of mammals as bloodstream forms, and in the midgut of Tsetse flies as procyclic forms. We show here that a single RNA-binding protein, RBP10, promotes the bloodstream-form trypanosome differentiation state. Depletion of RBP10 from bloodstream-form trypanosomes gives cells that can grow only as procyclic forms; conversely, expression of RBP10 in procyclic forms converts them to bloodstream forms. RBP10 binds to procyclic-specific mRNAs containing an UAUUUUUU motif, targeting them for translation repression and destruction. Products of RBP10 target mRNAs include not only the major procyclic surface protein and enzymes of energy metabolism, but also protein kinases and stage-specific RNA-binding proteins: this suggests that alterations in RBP10 trigger a regulatory cascade.

【 授权许可】

CC BY