4.8 Article

An RNA-binding protein complex regulates the purine-dependent expression of a nucleobase transporter in trypanosomes

Journal

NUCLEIC ACIDS RESEARCH
Volume 49, Issue 7, Pages 3814-3825

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab181

Keywords

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Funding

  1. Ministerio de Economia, Industria y Competitividad [BFU2014-55193-P]
  2. Spanish National Research Council (CSIC) [201920E114]
  3. CSIC Open Access Publication Support Initiative, Unit of Information Resources for Research (URICI)

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The study identified a protein complex composed of PuREBP1 and PuREBP2 in Trypanosoma brucei that interacts with specific mRNAs to regulate gene expression, particularly in response to purines.
Post-transcriptional regulation of gene expression is particularly important in trypanosomatid protozoa. RNA-binding proteins (RBPs) regulate mRNA stability and translation, yet information about how RBPs are able to link environmental cues to post-transcriptional control is scarce. In Trypanosoma brucei, we have previously characterized a short RNA stem-loop cis-element (PuRE, Purine Responsive Element) within the 3'-UTR of the NT8 nucleobase transporter mRNA that is necessary and sufficient to confer a strong repression of gene expression in response to purines. In this study, we have identified a protein complex composed of two RNA-binding proteins (PuREBP1 and PuREBP2) that binds to the PuRE in vitro and to NT8 mRNA in vivo. Depletion of PuREBP1 by RNA interference results in the upregulation of just NT8 and the mRNAs encoding the amino acid transporter AATP6 paralogues. Moreover, we found that the PuREBP1/2 complex is associated with only a handful of mRNAs, and that it is responsible for the observed purine-dependent regulation of NT8 expression.

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