Mechanisms and Evolution of tRNA 5′-Editing in Mitochondria
In several protists and fungi, many of the tRNAs encoded by the mitochondrial genome are unusual in that they are predicted to have mismatches within the first three positions of the acceptor stem. However, examination of the sequences of the corresponding mature tRNAs has shown that these positions instead contain canonical Watson-Crick-type base pairs. This difference results from changes that are made at the transcript level, such that predicted mismatches are effectively corrected. The correction process, termed mitochondrial tRNA 5′-editing (mt-tRNA 5′-editing), involves removal in the 5′-to-3′ direction of several nucleotides, starting at the 5′-end of the acceptor stem and including those 5′ nucleotides at positions of mismatching, followed by sequential addition of nucleotides in the 3′-to-5′ direction to fill in the resulting gap, with nucleotides on the 3′ side of the stem serving to guide incorporation. While the nature of the nuclease(s) involved in removal of nucleotides during mt-tRNA 5′-editing is unknown, the addition function is carried out by a mitochondrion-targeted Thg1-like protein (TLP), a novel 3′-to-5′ nucleotidyltransferase (“reverse RNA polymerase”). Thg1 (tRNA-histidine guanylyltransferase), the founding member of the protein family to which TLPs also belong, catalyzes the addition of a single, non-templated G residue to the 5′-end of histidine tRNA, whereas TLPs involved in mt-tRNA 5′-editing robustly catalyze multiple rounds of templated addition of nucleotides to the 5′-end of appropriately truncated tRNA substrates. To date, mt-tRNA 5′-editing has been experimentally documented in several amoebozoan and fungal species and is predicted to occur in several other protist lineages. Consideration of phylogenetic distribution and biochemical characteristics suggests a constructive neutral evolution (CNE) scenario for the evolution of mt-tRNA 5′-editing, wherein mitochondrion-targeted TLPs independently emerge in discrete eukaryotic lineages, thereby allowing the fixation in the mitochondrial genome of tRNA mismatch mutations that would otherwise be purged by purifying selection.
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