The Martinez group focuses in themes of RNA metabolism. Our strategy is novel in that we use siRNAs as substrates to discover enzymes that phosphorylate and ligate RNA molecules. With this approach we have identified Clp1, a component of the tRNA splicing and mRNA 3’ end formation machineries as the first human RNA-kinase. We have recently uncovered a second nucleic-acid kinase, which localizes at the nucleolus. On the other hand, RNA-ligases remain mysterious in human cells. Searching for the elusive human tRNA ligase, we have purified an activity that ligates siRNAs displaying similar termini as 5’ and 3’ tRNA exons. Another challenging project is to reveal the enzyme that re-ligates Xbp1 mRNA, in a non-canonical splicing event, during the Unfolded Protein Response. For this, we have performed a genome-wide RNAi screen in Drosophila cells. We would like to understand the mechanism of action of these enzymes and identify their cellular substrates. With these new players in hand we will re-visit, with a distinctive angle, processes such as tRNA splicing, mRNA 3’ end formation and ribosomal RNA processing, and further explore connections between them.

To study the biology of RNA-kinases and RNA-ligases, we combine: chromatography and genome-wide RNAi screens at the discovery phase; in vitro and in silico experiments to understand molecular mechanisms; deep sequencing to identify RNA substrates, and in vivo studies to analyze the phenotype of knock-out and knock-in mice.

Contact:

Javier Martinez
Group Leader
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