Enzymology, targets and function of RNA-terminal modifications
The Martinez Lab studies the function and the structure of the mammalian enzymes that execute and regulate pre-tRNA splicing and the cytoplasmic splicing of Xbp1-mRNA during the Unfolded Protein Response (UPR).
The Martinez Lab has identified and characterized the 5’ RNA-kinase CLP1, the tRNA ligase complex and its essential cofactor Archease and, very recently, the first RNA 2’,3’-cyclic phosphatase described in human cells, previously thought to be an enzyme that removes poly(A) tails. In terms of regulation, the spotlight is on the unexpected inhibition of the tRNA ligase complex by oxidative stress, and the protection exerted by a novel oxido-reductase that causes severe myopathies when mutated.
Within RNA-DECO, and by applying CLIP and high-throughput sequencing approaches, the Martinez Lab aims at identifying RNA targets for CLP1 and the 2’,3’-cyclic phosphatase. Modulating the expression levels of these enzymes, both in normal and stress conditions, should lead to changes in the dynamics of RNA terminal modifications and, ultimately, in the fate of target RNAs.