Javier Martinez

Picture of the Group Leader Javier Martinez

RNA metabolism in mammalian cells

  • In mice and humans some tRNAs are exclusively encoded as intron-containing genes, thus highlighting the importance of tRNA splicing as an essential process. Introns are excised in the nucleus by the tRNA splicing endonuclease (TSEN) complex. The resulting exon halves are subsequently ligated to generate mature tRNAs. We have combined chromatography, mass spectrometry, RNAi and phylogenetic analysis to identify key components of the human tRNA splicing pathway, and discovered the RNA kinase CLP1 as part of the TSEN complex (S. Weitzer and J. Martinez, 2007). We also discovered the tRNA ligase complex which has been elusive for 30 years, established RTCB/HSPC117 as the catalytic subunit (J. Popow et al., 2011 and 2012), and archease as an essential co-factor of the tRNA ligase complex (J. Popow et al., 2014).

    Recently we showed that the tRNA ligase and archease play critical roles in the unfolded protein response and that CLP1, when mutated, causes neurological diseases both in humans and mice. In this annual report we describe the unexpected sensitivity of the tRNA ligase complex to oxidative stress and our attempts to identify a novel RNA processing activity associated with the mammalian RNA 3’ phosphate cyclase RTCD1.

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    Javier Martinez
    Group Leader
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Javier Martinez is currently moving his lab to the Medical University of Vienna

 

 

Selected Publications

(2014)
 
Karaca, E., Weitzer, S., Pehlivan, D., Shiraishi, H., Gogakos, T., Hanada, T., Jhangiani, SN., Wiszniewski, W., Withers, M., Campbell, IM., Erdin, S., Isikay, S., Franco, LM., Gonzaga-Jauregui, C., Gambin, T., Gelowani, V., Hunter, JV., Yesil, G., Koparir, E., Yilmaz, S., Brown, M., Briskin, D., Hafner, M., Morozov, P., Farazi, TA., Bernreuther, C., Glatzel, M., Trattnig, S., Friske, J., Kronnerwetter, C., Bainbridge, MN., Gezdirici, A., Seven, M., Muzny, DM., Boerwinkle, E., Ozen, M., Clausen, T., Tuschl, T., Yuksel, A., Hess, A., Gibbs, RA., Martinez, J., Penninger, JM., Lupski, JR. (2014). Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function. Cell. 157(3):636-50 (abstract)
 
(2013)
 
Hanada, T., Weitzer, S., Mair, B., Bernreuther, C., Wainger, BJ., Ichida, J., Hanada, R., Orthofer, M., Cronin, SJ., Komnenovic, V., Minis, A., Sato, F., Mimata, H., Yoshimura, A., Tamir, I., Rainer, J., Kofler, R., Yaron, A., Eggan, KC., Woolf, CJ., Glatzel, M., Herbst, R., Martinez, J., Penninger, JM. (2013). CLP1 links tRNA metabolism to progressive motor-neuron loss. Nature. 495(7442):474-80 (abstract)
 
(2012)
 
Popow, J., Schleiffer, A., Martinez, J. (2012). Diversity and roles of (t)RNA ligases. Cell Mol Life Sci. 69(16):2657-70 (abstract)
 
(2011)
 
Popow, J., Englert, M., Weitzer, S., Schleiffer, A., Mierzwa, B., Mechtler, K., Trowitzsch, S., Will, CL., Lührmann, R., Söll, D., Martinez, J. (2011). HSPC117 is the essential subunit of a human tRNA splicing ligase complex. Science. 331(6018):760-4 (abstract)
 
(2007)
 
Weitzer, S., Martinez, J. (2007). The human RNA kinase hClp1 is active on 3' transfer RNA exons and short interfering RNAs. Nature. 447(7141):222-6 (abstract)
 

NETWORKING:

The Vienna Biocenter in the third district of Vienna has established itself as the premier location for life sciences in Central Europe and is a world-leading international bio-medical research center.

 

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