RNAi, the guiding principle and keeping family happy

RNA 2015 Apr;21(4):555-6. doi: 10.1261/rna.049635.115.

JD Alfonzo

I am a relative newcomer to the RNA field and have knowingly worked on RNA since 1995. You may say that my interest in RNA literally started with the RNA journal. Having to choose my favorite topic in RNA in the last 20 years is worse than asking a good parent to choose a favorite child. What compounds the problem is that in this particular case the “family” is quite extensive and includes, in the last 20 years alone, 612,536 siblings (entries in PubMed) that harbor the word “RNA.” Nonetheless, at the risk of offending my extensive and extended family, choose I must. For me the single most important discovery has to meet two major, yet simple, criteria: 1) it must impact fields beyond that from which the discovery was made; 2) it must generate a principle or concept that can be applicable to thinking about other unresolved scientific questions. Additionally, the discovery may, if providence allows, have some practical applications, although this last point need not be an absolute requirement.

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A common tRNA modification at an unusual location: the discovery of wyosine biosynthesis in mitochondria.

Nucleic Acids Res. 2015 Apr 30;43(8):4262-73. doi: 10.1093/nar/gkv286. Epub 2015 Apr 6.

Sample PJ¹, Kořený L², Paris Z¹, Gaston KW³, Rubio MA¹, Fleming IM¹, Hinger S¹, Horáková E², Limbach PA³, Lukeš J⁴, Alfonzo JD⁵.

Abstract

Establishment of the early genetic code likely required strategies to ensure translational accuracy and inevitably involved tRNA post-transcriptional modifications. One such modification, wybutosine/wyosine is crucial for translational fidelity in Archaea and Eukarya; yet it does not occur in Bacteria and has never been described in mitochondria. Here, we present genetic, molecular and mass spectromery data demonstrating the first example of wyosine in mitochondria, a situation thus far unique to kinetoplastids. We also show that these modifications are important for mitochondrial function, underscoring their biological significance. This work focuses on TyW1, the enzyme required for the most critical step of wyosine biosynthesis. Based on molecular phylogeny, we suggest that the kinetoplastids pathways evolved via gene duplication and acquisition of an FMN-binding domain now prevalent in TyW1 of most eukaryotes. These findings are discussed in the context of the extensive U-insertion RNA editing in trypanosome mitochondria, which may have provided selective pressure for maintenance of mitochondrial wyosine in this lineage. 

© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.