Key result
RNAi silencing of MRB1 subunits blocks Trypanosoma brucei cell growth and guide RNA expression.
Why the study?
The role of mitochondrial RNA binding complex 1 subunits in guide RNA biogenesis and RNA editing in Trypanosoma brucei was not fully understood.
Identifies essential subunits of the MRB1 complex required for guide RNA biogenesis and RNA editing in Trypanosoma brucei.
May nominate MRB1 subunits as antiparasitic targets; leaves open druggability and host selectivity.
The mitochondrial RNA binding complex 1 (MRB1) is a recently discovered complex of proteins associated with the TbRGG1 and TbRGG2 proteins in Trypanosoma brucei. Based on the phenotype caused by down-regulation of these two proteins, it was proposed to play an unspecified role in RNA editing. RNAi silencing of three newly characterized protein subunits, guide RNA associated proteins (GAPs) 1 and 2 as well as a predicted DExD/H-box RNA helicase, show they are essential for cell growth in the procyclic stage. Furthermore, their down-regulation leads to inhibition of editing in only those mRNAs for which minicircle-encoded guide (g) RNAs are required. However, editing remains unaffected when the maxicircle-encoded cis-acting gRNA is employed. Interestingly, all three proteins are necessary for the expression of the minicircle-encoded gRNAs. Moreover, down-regulation of a fourth assayed putative MRB1 subunit, Nudix hydrolase, does not appear to destabilize gRNAs, and down-regulation of this protein has a general impact on the stability of maxicircle-encoded RNAs. GAP1 and 2 are also essential for the survival of the bloodstream stage, in which the gRNAs become eliminated upon depletion of either protein. Immunolocalization revealed that GAP1 and 2 are concentrated into discrete spots along the mitochondrion, usually localized in the proximity of the kinetoplast. Finally, we demonstrate that the same mtRNA polymerase known to transcribe the maxicircle mRNAs may also have a role in expression of the minicircle-encoded gRNAs.
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Hashimi et al. (2009) studied Trypanosoma brucei infection / Basic science. RNAi silencing of MRB1 subunits (GAP1, GAP2, DExD/H-box RNA helicase) was evaluated on Cell growth, RNA editing, and guide RNA expression. RNAi silencing of MRB1 subunits GAP1, GAP2, and a DExD/H-box RNA helicase in Trypanosoma brucei demonstrated they are essential for cell growth and minicircle-encoded guide RNA expression.
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