RT Journal Article
SR Electronic
T1 The RNA-binding protein RBP10 controls a regulatory cascade that defines bloodstream-form trypanosome identity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 076273
DO 10.1101/076273
A1 Elisha Mugo
A1 Christine Clayton
YR 2016
UL http://biorxiv.org/content/early/2016/09/20/076273.abstract
AB Gene expression control in the pathogen Trypanosoma brucei 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, defines 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: consequently, alterations in RBP10 trigger a regulatory cascade.