We are a medium-sized group (~15 people) of enthusiastic, passionate and hard-working “musicians” from post-docs to undergraduate students with one skillful lab assistant, who are eager to learn more and more every day while having fun at the same time. Our recording studio is based at the Institute of Microbiology (IMIC) of the Czech Academy of Sciences (CAS) in Prague, Czech Republic.

Our band nicknamed Laboratory of Regulation of Gene Expression  (LRGE) was established in June 2006 and investigates fundamentals of one of the key, life-giving molecular processes in the cell and its regulation at both general as well as gene-specific levels. We R talking about protein synthesis! Simply speaking, our mostly basic research is focused on figuring out how the cell deciphers the genetic code of DNA using relatively simple decoding keys and uses this gene-encoded information to produce proteins, i.e., cellular effectors, through a very complex process also called translation.

Recently, we have become very much interested in various alternatives to these decoding keys, so-called alternative genetic codes, the detailed knowledge of which could be exploited in the treatment of various genetic diseases. In addition, we are interested in understanding how translation is regulated in response to constantly changing environmental conditions that the cell faces and to which it must immediately respond in order to adapt its repertoire of proteins that it is currently producing.

As for the importance of our research from the socio-economic and medical perspectives, we want to broaden and deepen the general understanding of how these basic cellular processes properly operate in the cell, so that our collaborators who are primarily interested in applied research; i.e., research directly aimed at developing the most appropriate treatment for a particular disease, can feed from it while investigating various pathologies. 

Overall, paying the utmost tribute to our distinguished ancient predecessors, our major goal is to help to transmute lead ( basic research discoveries) into gold (useful therapeutics) with the simplest and finest tones.

Our compositions combine the use of mammalian cells lines and partly also the budding yeast Saccharomyces cerevisiae model organism and employ tools of molecular and structural biology, biochemistry and genetics. 

We also very much enjoy participating in numerous popularization gigs (like Open Science, Researcher’s Night, etc.), giving interviews to news and radio, contributing to popularization magazines, etc. 

Our band won “The best original research publication carried out at the Institute of Microbiology CAS Award” (our home institute) in years 2008, 2011, 2013, 2015, 2016, 2017, 2018, 2019, 2020, 2021, and 2022. In February 2016, the international evaluation committee selected our band as one of the 13 most prestigious ones in the entire CAS.

Our recording is (or until recently was) supported by the national and world renowned funding bodies such as the the Wellcome Trust, Howard Hughes Medical Institute, NIH FIC, German Science Foundation, Czech Science Foundation and Czech Academy of Sciences (Praemium Academiae). Altogether, we have produced >75 records with record labels like Nature (see our winning cover page),  Molecular Cell, Nature Protocols, Nucleic Acids Research, Genes & Development, EMBO J., eLife, etc. Music is always composed by LRGE, lyrics usually by LSV.

Top records since we first took the stage.

1. Smirnova, A. M., Hronová, V., Mohammad, M. P., Herrmannová, A., Gunišová, S., Petráčková, D., Halada, P., Coufal, Š., Świrski, M., Rendleman, J., Jendruchová, K., Hatzoglou, M., Beznosková, P., Vogel, C.*, Valášek, L.S.*^$ (2024). Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control. Cell reports, 43,(4), 113976. https://doi.org/10.1016/j.celrep.2024.113976

 

2. Kachale, A.^#, Pavlíková, Z.^#, Nenarokova, A.^#, Roithová, A., Durante, I.M., Miletínová, P., Záhonová, K., Nenarokov, S., Votýpka, J., Horáková, E., Ross, L.R., Yurchenko, V., Beznosková, P., Paris, Z*, Valášek, L.S.*^$, and Lukeš, J.* (2023) Short tRNA anticodon stem with mutant eRF1 allow stop codon reassignment.  Nature, 613, 751-758. https://pubmed.ncbi.nlm.nih.gov/36631608/

 

3. Wagner, S.^#, Bohlen, J.^#, Herrmannová, A.^#, Jelínek, J., Preiss, T.*, Valášek, L.S.*, and Teleman, A.* (2022) Selective footprinting of 40S and 80S ribosome subpopulations (Sel-TCP-seq) to study translation and its control. Nat Prot., 17,(10), 2139-2187. https://doi.org/10.1038/s41596-022-00708-4

 

4. Beznosková, P.*, Bidou, L., Namy, O., and Valášek, L.S.* (2021) Increased expression of tryptophan and tyrosine tRNAs elevates stop codon readthrough of reporter systems in human cell lines. Nucleic Acids Res., 49, (9), 5202-5215. https://doi.org/10.1093/nar/gkab315

 

5. Wagner, S.*, Herrmannová, A., Hronová, V., Gunišová, S., Sen, N., Hannan, R.D., Hinnebusch, A.G., Shirokikh, N.E., Preiss, T.*, and Valášek, L.S.*^$ (2020) Selective translation complex profiling reveals staged initiation and co-translational assembly of initiation factor complexes. Mol. Cell, 79, (4), 546-560.e7. https://doi.org/10.1016/j.molcel.2020.06.004

 

6.  Herrmannová, A.*, Prilepskaja, T., Wagner, S., Šikrová, D., Zeman, J., Poncová, K., and Valášek, L.S.* (2020) Adapted formaldehyde gradient cross-linking protocol implicates human eIF3d and eIF3c, k and l subunits in the 43S and 48S pre-initiation complex assembly, respectively. Nucleic Acids Res., 48, (4), 1969-1984. https://doi.org/10.1093/nar/gkz1185

 

7. Beznosková, P.*, Pavlíková, Z., Zeman, J., Aitken, C.E., and Valášek, L.S.* (2019) Yeast applied readthrough inducing system (YARIS): An in vivo assay for the comprehensive study of translational readthrough. Nucleic Acids Res., 47(12), 6339-6350. https://doi.org/10.1093/nar/gkz346

 

8. Guan, B-J., van Hoef, V., Jobava, R., Elroy-Stein, O., Valášek, L.S., Cargnello, M., Gao, X-H., Krokowski, D., Merrick, W.C., Kimball, S.R., Komar, A.A., Koromilas, A.E., Wynshaw-Boris, A., Topisirovic, I.*, Larsson, O.*, and Hatzoglou, M.* (2017) A unique ISR program determines cellular responses to chronic stress. Mol Cell, 68 (5), 885-900. https://doi.org/10.1016/j.molcel.2017.11.007

 

9. Valášek, L.S.*, Zeman, J., Wagner, S., Beznosková, P., Pavlíková, Z., Mohammad, M.P., Hronová, V., Herrmannová, A., Hashem, Y., and Gunišová, S. (2017) Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle. Nucleic Acids Res., 45 (19), 10948-10968, Epub 2017 Sep 14. https://doi.org/10.1093/nar/gkx805

 

10. Mohammad, M.P., Munzarová Pondělíčková, V., Zeman, J., Gunišová, S., and Valášek, L.S.* (2017) In vivo evidence that eIF3 stays bound to ribosomes elongating and terminating on short upstream ORFs to promote reinitiation. Nucleic Acids Res., 45 (5), 2658-2674, Epub 2017 Jan 24. https://doi.org/10.1093/nar/gkx049

 

11. Wagner, S., Herrmannová, A., Šikrová, D., and Valášek, L.S.* (2016) Human eIF3b and eIF3a serve as the nucleation core to assemble the remaining eIF3 subunits into two interconnected modules – the yeast-like core and the octamer. Nucleic Acids Res., 44 (22), 10772-10788, Epub 2016 Oct 19. https://doi.org/10.1093/nar/gkw972

 

12. Beznosková, P., Wagner, S., Jansen, M.E., von der Haar, T. and Valášek, L.S.* (2015) Translation initiation factors eIF3 promotes programmed stop codon readthrough. Nucleic Acid Res., 43(10), 5099-111. Epub 2015 April 29. https://doi.org/10.1093/nar/gkv421

 

13. Beznosková, P.^#, Cuchalová, L. ^#, Wagner, S., Shoemaker, C.J., Gunišová, S., von der Haar, T. and Valášek, L.S.* (2013) Translation initiation factors eIF3 and HCR1 control translation termination and stop codon read-through in yeast cells. PLoS Genet., 9, e1003962. https://doi.org/10.1371/journal.pgen.1003962

 

14. Valášek, L.S.* (2012) ’Ribozoomin’ – Translation Initiation from the Perspective of the ribosome-bound Eukaryotic Initiation Factors (eIFs). Curr Protein Pept Sci., 13, 305-330. https://doi.org/10.2174/138920312801619385

 

15. Kouba, T., Rutkai, E., Karasková, M., and Valášek, L.S.* (2012) The eIF3c/NIP1 PCI Domain Interacts with RNA and RACK1/ASC1 and Promotes Assembly of Translation Pre-initiation Complexes. Nucleic Acids Res., 40(6), 2683-99. Epub 2011 Nov 28. https://doi.org/10.1093/nar/gkr1083

 

16. Herrmannová, A.^#, Daujotytė, D.^#, Yang, J-C., Cuchalová, L., Gorrec, F., Wagner, S., Dányi, I., Lukavsky, P.J.*, and Valášek, L.S.* (2012) Structural Analysis of an eIF3 Subcomplex Reveals Conserved Interactions Required for a Stable and Proper Translation Pre-Initiation Complex Assembly. Nucleic Acids Res., 40(5), 2294-311. Epub 2011 Nov 15. https://pubmed.ncbi.nlm.nih.gov/22090426/

 

17. Munzarová, V., Pánek, J., Gunišová, S., Danyi, I., Szamecz, B. and Valášek, L.S.* (2011) Translation Reinitiation Relies on the Interaction Between eIF3a/TIF32 and Progressively Folded cis-acting mRNA Elements Preceding Short uORFs. PLoS Genet., 7, e1002137. https://doi.org/10.1371/journal.pgen.1002137

 

18. Cuchalová, L., Kouba, T., Herrmannová, A., Danyi, I., Chiu, W.-l. and Valášek, L.* (2010) The RNA Recognition Motif of Eukaryotic Translation Initiation Factor 3g (eIF3g) Is Required for Resumption of Scanning of Posttermination Ribosomes for Reinitiation on GCN4 and Together with eIF3i Stimulates Linear Scanning. Mol Cell Biol., 30, 4671-4686. https://doi.org/10.1128/mcb.00430-10

 

19. Szamecz, B., Rutkai, E., Cuchalová, L., Munzarová, V., Herrmannová, A., Nielsen, K.H., Burela, L., Hinnebusch, A.G., and Valášek, L.* (2008) eIF3a cooperates with sequences 5' of uORF1 to promote resumption of scanning by post-termination ribosomes for reinitiation on GCN4 mRNA. Genes & Dev., 22, 2414-2425. https://doi.org/10.1101/gad.480508

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