Talk abstracts

Talk on Saturday 09:00-09:15am submitted by Paul Sample

A Common Modification in an Unusual Place: Avoiding Conundrums in Mitochondrial Translation

Paul Sample (Microbiology - The Ohio State University), Ludek Koreny (Biology Centre, Institute of Parasitology, Czech Academy of Sciences), Zdenek Paris (Microbiology - The Ohio State University), Julius Lukes (Biology Centre, Institute of Parasitology, Czech Academy of Sciences), Juan Alfonzo (Microbiology - The Ohio State University)

Abstract:
Trypanosomes perform RNA editing, one of the most bizarre biochemical processes, in which the transcripts of mitochondrial genes are made translatable after extensive site-specific insertion and deletion of uridines. Editing in turn also creates uridine-rich mRNAs, whereby, in order to restore open-reading frames, poly-uridines often occur within coding regions. A potential problem of translation accuracy then makes itself apparent following well-documented cases in other eukaryotes, where multiple consecutive uridines in mRNA can lead to -1 ribosomal frameshifting; creating nonfunctional polypeptides. Since the codon UUU codes for phenylalanine, correct reading frame maintenance at repeated phenylalanine codons requires the presence of the hyper-modified nucleotide wybutosine 3’ of the anticodon (position 37) of phenylalanyl tRNA. In its most common form seen in eukaryotes, wybutosine is the product of five highly conserved wybutosine-synthesizing enzymes that use a guanosine (G37) precursor.
We have hypothesized that in systems that undergo massive mRNA editing, such as the trypanosome mitochondria, similar mechanisms must exist to prevent frameshifting and ensure fidelity during translation. However, wybutosine has not been reported in the mitochondrial tRNAs of any organism. In the present work, we show that mitochondrial tRNAPhe undergoes unusual modifications at position 37 and in addition nearly all of the wybutosine-synthesizing machinery has been duplicated in the trypanosome mitochondria, suggesting a potential role in reading frame maintenance and lending credence to our proposed hypothesis.

References:
de Crecy-Lagard, V., et al.

Keywords: tRNA, Wybutosine, Trypanosome