Uridine insertion/deletion editing in trypanosomes: a playground for RNA-guided information transfer

Authors

  • Ruslan Aphasizhev,

    Corresponding author
    1. Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA, USA
    • Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA, USA
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  • Inna Aphasizheva

    1. Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA, USA
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Abstract

RNA editing is a collective term referring to enzymatic processes that change RNA sequence apart from splicing, 5′ capping or 3′ extension. In this article, we focus on uridine insertion/deletion mRNA editing found exclusively in mitochondria of kinetoplastid protists. This type of editing corrects frameshifts, introduces start and stops codons, and often adds much of the coding sequence to create an open reading frame. The mitochondrial genome of trypanosomatids, the most extensively studied clade within the order Kinetoplastida, is composed of ∼50 maxicircles with limited coding capacity and thousands of minicircles. To produce functional mRNAs, a multitude of nuclear-encoded factors mediate interactions of maxicircle-encoded pre-mRNAs with a vast repertoire of minicircle-encoded guide RNAs. Editing reactions of mRNA cleavage, U-insertions or U-deletions, and ligation are catalyzed by the RNA editing core complex (RECC, the 20S editosome) while each step of this enzymatic cascade is directed by guide RNAs. These 50–60 nucleotide (nt) molecules are 3′ uridylated by RET1 TUTase and stabilized via association with the gRNA binding complex (GRBC). Remarkably, the information transfer between maxicircle and minicircle transcriptomes does not rely on template-dependent polymerization of nucleic acids. Instead, intrinsic substrate specificities of key enzymes are largely responsible for the fidelity of editing. Conversely, the efficiency of editing is enhanced by assembling enzymes and RNA binding proteins into stable multiprotein complexes. WIREs RNA 2011 2 669–685 DOI: 10.1002/wrna.82

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