Dynamics of translation under normal conditions and oxidative stress
Final Report Abstract
The major goal of this sub-project was to understand with mechanistic details and precision the effect of translation on cellular proteome and protein expression and the effect of oxidative stress on the the integrity of translation components in both eukaryotes and prokaryotes. The most important achievements and discoveries from this project are: (1) the discovery of new structural signatures in bacterial mRNAs that shape gene expression; (2) the novel finding that a silent polymorphism (sSNP) in eukaryotic protein, usually considered as neutral for protein function as it changes a codon but not the encoded amino acid, and this sSNP alters protein expression and function by locally changing the speed of mRNA translation in tRNA and tissue-specific manner; (3) the mechanistic insights on ribosome assembly, ribosomal hybernation and tRNA integrity under nutrient limitations in E. coli, and tRNA integrity under oxidative stress in eukaryotic cells; (4) the identification of previously unappreciated mechanism of m6A modification in triaging mRNAs into stress granules which expands the breadth of physiological roles of m6A modifications; and (5) the mechanistic differences in translation in mitotic and postmitotic tissues. The project led to several fruitful collaborations with other members of FOR1805 (Ned Budisa, Cristian Spahn and Daniel Wilson) which resulted in joint publications.
Publications
- The RNA-binding protein Hfq is important for ribosome biogenesis and affects translation fidelity. EMBO J. 37, e97631 (2018)
Andrade, J.M., dos Santos, R.F., Chelysheva, I., Ignatova Z. and Arraiano, C.M.
(See online at https://doi.org/10.15252/embj.201797631) - Reversible and rapid transfer-RNA deactivation as a mechanism of translational repression in stress. PLoS Genet. 9, e1003767 (2013)
Czech, A., Wende, S., Mörl, M., Pan, T., and Ignatova Z.
(See online at https://doi.org/10.1371/journal.pgen.1003767) - Emerging roles of tRNA in adaptive translation, signalling dynamics and disease. Nature Rev Genet, 16, 98-112 (2015)
Kirchner, S., Ignatova, Z.
(See online at https://doi.org/10.1038/nrg3861) - Secondary structure across the bacterial transcriptome reveals versatile roles in mRNA regulation and function. PLoS Genet. 11, e1005613 (2015)
Del Campo, C., Bartholomäus, A., Fedyunin, I. and Ignatova, Z.
(See online at https://doi.org/10.1371/journal.pgen.1005613) - An expanded CAG repeat in huntingtin causes +1 frameshifting. J Biol Chem. 291, 18505-13, (2016)
Saffert, P., Adamla, F., Schieweck, R., Atkins, J.F. and Ignatova Z.
(See online at https://doi.org/10.1074/jbc.M116.744326) - Discharging tRNAs: a tug of war between translation and detoxification in Escherichia coli. Nucl. Acids. Res. 44, 8324-8334 (2016)
Avcilar-Kucukgoze I, Bartholomäus A, Cordero Varela JA, Kaml RF, Neubauer P, Budisa N, Ignatova Z
(See online at https://doi.org/10.1093/nar/gkw697) - Alteration of protein function by a silent polymorphism linked to tRNA abundance. PLOS Biology 15, e2000779 (2017)
Kirchner, S., Cai, Z., Rauscher, R., Kastelic, N., Anding, M., Czech, A., Kleizen, B., Ostedgaard, L.S., Braakman, I., Sheppard, D.N. and Ignatova, Z.
(See online at https://doi.org/10.1371/journal.pbio.2000779) - Systematic probing of the bacterial RNA structurome to reveal new functions. Curr. Opin. Microbiol. 36, 14-19 (2017)
Ignatova, Z., and Narberhaus, F.
(See online at https://doi.org/10.1016/j.mib.2017.01.003) - Dynamic m6A methylation facilitates mRNA triaging to stress granules. Life Sci Alliance 1, e201800113 (2018)
Anders, M., Chelysheva, I., Goebel, I., Trenkner, T., Zhou, J., Mao, Y., Verzini, S., Qian, S.B. & Ignatova, Z.
(See online at https://doi.org/10.26508/lsa.201800113) - Structure of hybernating 100S ribosome reveals an inactive conformation of the ribosomal S1. Nature Microbiol. 3, 1115-1121 (2018)
Beckert, B., Turk, M., Czech, A., Berninghausen, O., Beckmann, R., Ignatova, Z., Plitzko, J.M. & Wilson, D.N.
(See online at https://doi.org/10.1038/s41564-018-0237-0)
