Trypanosome MKT1 and the RNA-binding protein ZC3H11: Interactions and potential roles in post-transcriptional regulatory networks

Aditi Singh, Igor Minia, Dorothea Droll, Abeer A. Fadda, Christine Clayton, Esteban Erben

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The trypanosome zinc finger protein ZC3H11 binds to AU-rich elements in mRNAs. It is essential for survival of the mammalian-infective bloodstream form, where it stabilizes several mRNAs including some encoding chaperones, and is also required for stabilization of chaperone mRNAs during the heat-shock response in the vector-infective procyclic form. When ZC3H11 was artificially 'tethered' to a reporter mRNA in bloodstream forms it increased reporter expression. We here show that ZC3H11 interacts with trypanosome MKT1 and PBP1, and that domains required for both interactions are necessary for function in the bloodstream-form tethering assay. PBP1 interacts with MKT1, LSM12 and poly(A) binding protein, and localizes to granules during parasite starvation. All of these proteins are essential for bloodstream-form trypanosome survival and increase gene expression in the tethering assay. MKT1 is cytosolic and polysome associated. Using a yeast two-hybrid screen and tandem affinity purification we found that trypanosome MKT1 interacts with multiple RNA-binding proteins and other potential RNA regulators, placing it at the centre of a post-transcriptional regulatory network. A consensus interaction sequence, H(E/D/N/Q)PY, was identified. Recruitment of MKT1-containing regulatory complexes to mRNAs via sequence-specific mRNA-binding proteins could thus control several different post-transcriptional regulons.

Original languageEnglish
Pages (from-to)4652-4668
Number of pages17
JournalNucleic Acids Research
Volume42
Issue number7
DOIs
Publication statusPublished - 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

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