Research
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Evolutionary Aspects of Ribosome Biogenesis
Ribosomes are universally conserved large ribonucleoprotein particles ensuring protein synthesis in every cell. The universal conservation of ribosome function and structure offers a unique paradigm for understanding how RNP assembly mechanisms and function have evolved. Consequently, deciphering the general principles and differences of ribosome synthesis and function across the different domains of life can contribute to a better understanding of the evolution history of these fundamental processes. However, to achieve such a level of understanding, it is necessary to define conserved and specific principles of the ribosome life cycle in model organisms representative of all domains of life. Whereas, ribosome synthesis has been well characterized in both bacteria and eukarya, the archaeal ribosome biogenesis pathway is, in contrast, still largely unexplored.
Remarkably, the lack of clear conservation between key ribosome biogenesis factors between bacteria and eukarya suggest that most of the ribosome biogenesis process has been almost reengineered in the course of the evolution. Interestingly, genomic and few in vitro analysis suggest the presence of few known bacterial and eukaryotic ribosomes biogenesis factors in archaeal genomes. Thus, suggesting that the archaeal ribosome biogenesis pathway might proceed via a mixture of bacterial and eukaryotic features to which archaeal specific features have been eventually implemented. Moreover, this also suggests that eukaryotic ribosome biogenesis might have evolved, to some extent, on the basis of a “simplified” archaeal ribosome biogenesis pathway. However, to further shed light on the evolution of this pathway, the fundamental molecular biology of this process still needs to be fully defined in any archaeon.
Therefore, to better characterize the ribosome biosynthesis pathway from an evolutionary perspective and to better understand the conserved molecular principles allowing efficient RNP assembly we are analyzing:
I) Ribosome biogenesis in Archaea
We aim to obtain a comprehensive molecular insights into the “Life” and “Death” of ribosomes in archaea. To this end we are using a multidisciplinary approach to:
- Define the pre-rRNA processing pathway and its dynamics.
- Define key cis- and trans-acting elements involved in ribosomal subunits maturation and determine their detailed molecular functions.
- Define the dynamics of assembly and disassembly of ribosomal precursors.
To achieve these goals we are mostly taking advantage of two genetically tractable model archaeon: the halophilic Euryarchaeota Haloferax volcanii and the thermo-acidophile Crenoarchaeota Sulfolobus acidocaldarius.
Further reading:
Knüppel R, Christensen RH, Gray FC, Esser D, Strauß D, Medenbach J, Siebers B, MacNeill SA, LaRonde N, Ferreira-Cerca S. Insights into the evolutionary conserved regulation of Rio ATPase activity. Nucleic Acids Res. 2018 Feb 16;46(3):1441-1456. doi: 10.1093/nar/gkx1236. PubMed PMID: 29237037.
Ferreira-Cerca S. Life and Death of Ribosomes in Archaea. In: Clouet-d'Orval B. (eds) RNA Metabolism and Gene Expression in Archaea. Nucleic Acids and Molecular Biology, 2017 vol 32. Springer, Cham. Print ISBN 978-3-319-65794-3. Online ISBN 978-3-319-65795-0.
Knüppel R, Kuttenberger C, Ferreira-Cerca S. Toward Time-Resolved Analysis of RNA Metabolism in Archaea Using 4-Thiouracil. Front Microbiol. 2017 Feb 24;8:286. doi: 10.3389/fmicb.2017.00286. eCollection 2017. PubMed PMID: 28286499; PubMed Central PMCID: PMC5323407.
II) Comparative structural & functional analysis of the evolutionary conserved RIO protein family in RNP biogenesis
The RIO & RIO-like proteins are evolutionary conserved atypical Kinases/ ATPases involved in the biosynthesis of the small ribosomal subunit and some tRNAs. We aim to better characterize the molecular mechanisms of the RIO protein family. To this end, we are performing comparative structural & functional analysis of the RIO protein family using several archaeal and eukaryotic model organisms.
Further reading:
Knüppel R, Christensen RH, Gray FC, Esser D, Strauß D, Medenbach J, Siebers B, MacNeill SA, LaRonde N, Ferreira-Cerca S. Insights into the evolutionary conserved regulation of Rio ATPase activity. Nucleic Acids Res. 2018 Feb 16;46(3):1441-1456. doi: 10.1093/nar/gkx1236. PubMed PMID: 29237037.
Ferreira-Cerca S, Kiburu I, Thomson E, LaRonde N, Hurt E. Dominant Rio1 kinase/ATPase catalytic mutant induces trapping of late pre-40S biogenesis factors in 80S-like ribosomes. Nucleic Acids Res. 2014 Jul;42(13):8635-47. doi: 10.1093/nar/gku542. Epub 2014 Jun 19. PubMed PMID: 24948609; PubMed Central PMCID: PMC4117770.
Ferreira-Cerca S, Sagar V, Schäfer T, Diop M, Wesseling AM, Lu H, Chai E, Hurt E, LaRonde-LeBlanc N. ATPase-dependent role of the atypical kinase Rio2 on the evolving pre-40S ribosomal subunit. Nat Struct Mol Biol. 2012 Dec;19(12):1316-23. doi: 10.1038/nsmb.2403. Epub 2012 Oct 28. PubMed PMID: 23104056; PubMed Central PMCID: PMC3515705.
Team
Sébastien Ferreira-Cerca | curriculum vitae |
Current mentees | |
Knüppel, Robert | PhD student |
Jüttner, Michael | PhD student |
Alexandre, Nicolas | PhD student |
Dielforder, Tom | Master student |
Liebl, Maximilian | Master student |
Previous mentees | |
Matthias Weiß (Biochemistry - BSc 2013 and MSc 2017– now: PhD student at Helmholz Center Munich) | |
Corinna Kuttenberger (Biochemistry - MSc 2015– now: application specialist at 2bind GmbH) | |
Robert Knüppel (Biology - MSc 2015 – now: PhD student Uni Regensburg) | |
Nina Ostheimer (Biology - BSc 2015 – last seen as MSc student at Uni Regensburg) | |
Michael Kern (Molecular Medicine - BSc 2016 – now: medical student at Uni Würzburg) | |
Hannah Medinger (Biology –BSc 2018) | |
Michael Jüttner (Biology – MSc 2018 – now PhD student Uni Regensburg) |
Sébastien Ferreira-Cerca - Short CV
2018 | University Teaching Certificate of the Bavarian Universities / Zertifikat Hochschullehre der Bayerischen Universitäten |
since 2013 | Academic staff member at the University of Regensburg (Germany), Department of Biochemistry III (Chair: H. Tschochner) |
2008 - 2012 | Postdoctoral Fellow at the University of Heidelberg (Germany), Biochemistry Center (BZH) (Lab: E. Hurt) |
2003 - 2008 | Doctoral Thesis (Dr. rer. nat.) at the University of Regensburg (Germany) Department of Biochemistry III (Chair: H. Tschochner) |
Publications
Schwarz T, Berkemer S, Bernhart S, Weiß M, Ferreira-Cerca S, Stadler P, Marchfelder A. Splicing Endonuclease Is an Important Player in rRNA and tRNA Maturation in Archaea. Front Microbiol. 2020 Nov 20. doi=10.3389/fmicb.2020.594838.
Schulze S, Adams Z, Cerletti M, De Castro R, Ferreira-Cerca S, Fufezan C, Giménez MI, Hippler M, Jevtic Z, Knüppel R, Legerme G, Lenz C, Marchfelder A, Maupin-Furlow J, Paggi RA, Pfeiffer F, Poetsch A, Urlaub H, Pohlschroder M. The Archaeal Proteome Project advances knowledge about archaeal cell biology through comprehensive proteomics. Nat Commun. 2020 Jun 19;11(1):3145. doi: 10.1038/s41467-020-16784-7. PMID: 32561711; PMCID: PMC7305310.
Knüppel R, Fenk M, Jüttner M, Ferreira-Cerca S. In Vivo RNA Chemical Footprinting Analysis in Archaea. Methods Mol Biol. 2020;2106:193-208. doi: 10.1007/978-1-0716-0231-7_12. PMID: 31889259.
Jüttner M, Weiß M, Ostheimer N, Reglin C, Kern M, Knüppel R, Ferreira-Cerca S. A versatile cis-acting element reporter system to study the function, maturation and stability of ribosomal RNA mutants in archaea. Nucleic Acids Res. 2020 Feb 28;48(4):2073-2090. doi: 10.1093/nar/gkz1156. PMID: 31828323; PMCID: PMC7038931.
Mitterer V, Shayan R, Ferreira-Cerca S*, Murat G, Enne T, Rinaldi D, Weigl S, Omanic H, Gleizes PE, Kressler D*, Plisson-Chastang C*, Pertschy B*. Conformational proofreading of distant 40S ribosomal subunit maturation events by a long-range communication mechanism. Nat Commun. 2019 Jun 21;10(1):2754. doi: 10.1038/s41467-019-10678-z. PMID: 31227701; PMCID: PMC6588571.
* joint corresponding
Linnemann J, Pöll G, Jakob S, Ferreira-Cerca S, Griesenbeck J, Tschochner H, Milkereit P. Impact of two neighbouring ribosomal protein clusters on biogenesis factor binding and assembly of yeast late small ribosomal subunit precursors.PLoS One. 2019 Jan 17;14(1):e0203415. doi: 10.1371/journal.pone.0203415.eCollection 2019. PubMed PMID: 30653518; PubMed Central PMCID: PMC6336269.
Berto G, Ferreira-Cerca S, De Wulf P. The Rio1 protein kinases/ATPases:
conserved regulators of growth, division, and genomic stability. Curr Genet. 2018 Dec 4. doi: 10.1007/s00294-018-0912-y. [Epub ahead of print] Review. PubMed PMID:30515528.
Iacovella MG, Bremang M, Basha O, Giacò L, Carotenuto W, Golfieri C, Szakal B,Dal Maschio M, Infantino V, Beznoussenko GV, Joseph CR, Visintin C, Mironov AA,Visintin R, Branzei D, Ferreira-Cerca S, Yeger-Lotem E, De Wulf P. Integrating Rio1 activities discloses its nutrient-activated network in Saccharomyces cerevisiae. Nucleic Acids Res. 2018 Sep 6;46(15):7586-7611. doi:10.1093/nar/gky618. PubMed PMID: 30011030; PubMed Central PMCID: PMC6125641.
Knüppel R, Christensen RH, Gray FC, Esser D, Strauß D, Medenbach J, Siebers B, MacNeill SA, LaRonde N, Ferreira-Cerca S. Insights into the evolutionary conserved regulation of Rio ATPase activity. Nucleic Acids Res. 2018 Feb 16;46(3):1441-1456. doi: 10.1093/nar/gkx1236. PubMed PMID: 29237037.
Ferreira-Cerca S. Life and Death of Ribosomes in Archaea. In: Clouet-d'Orval B. (eds) RNA Metabolism and Gene Expression in Archaea. Nucleic Acids and Molecular Biology, 2017 vol 32. Springer, Cham. Print ISBN 978-3-319-65794-3. Online ISBN 978-3-319-65795-0.
Knüppel R, Kuttenberger C, Ferreira-Cerca S. Toward Time-Resolved Analysis of RNA Metabolism in Archaea Using 4-Thiouracil. Front Microbiol. 2017 Feb 24;8:286. doi: 10.3389/fmicb.2017.00286. eCollection 2017. PubMed PMID: 28286499; PubMed Central PMCID: PMC5323407.
Iacovella MG, Golfieri C, Massari LF, Busnelli S, Pagliuca C, Dal Maschio M, Infantino V, Visintin V, Mechtler K, Ferreira-Cerca S, and De Wulf P. The Rio1 kinase downregulates RNA polymerase I to promote rDNA stability and segregation. Nature Communications in press.
Ferreira-Cerca S#*, Kiburu, I#, Thomson E, LaRonde N*, Hurt E*. Dominant Rio1 kinase/ATPase catalytic mutant induces trapping of late pre-40S biogenesis factors in 80S-like ribosomes. Nucleic Acids Research. 2014 Jun 19.
Thomson E#*, Ferreira-Cerca S#*, Hurt E. Eukaryotic ribosome biogenesis at a glance. J. Cell Sci. 2013 Nov 1;126(Pt 21):4815-21.
Ferreira-Cerca S#, Sagar V#, Schäfer T, Diop M, Wesseling AM, Lu H, Chai E, Hurt E, Laronde-Leblanc N. ATPase-dependent role of the atypical kinase Rio2 on the evolving pre-40S ribosomal subunit. Nat. Struct. Mol. Biol. 2012 Dec;19(12):1316-23.
Ferreira-Cerca S, Hurt E. Cell biology: Arrest by ribosome. Nature. 2009 May 7;459(7243):46-7. doi: 10.1038/459046a. PubMed PMID: 19424147.
Ferreira-Cerca S, Pöll G, Kühn H, Neueder A, Jacob S, Tschochner H, Milkereit P. Analysis of the in vivo assembly pathway of eukaryotic 40S ribosomal proteins. Mol. Cell. 2007 Nov 9;28 (3):446-457.
Ferreira-Cerca S, Pöll G, Gleizes PE, Tschochner H, Milkereit P. Roles of eukaryotic ribosomal proteins in maturation and transport of pre-18S rRNA and ribosome function. Mol. Cell. 2005 Oct 28;20 (2):263-75.
Leger-Silvestre I, Milkereit P, Ferreira-Cerca S, Saveanu C, Rousselle JC, Choesmel V, Guinefoleau C, Gas N, Gleizes PE. The ribosomal protein Rps15p is required for nuclear exit of the 40S subunit precursors in yeast. EMBO J. 2004 Jun 16;23 (12):2336-47.
# joint first authors. * joint corresponding authors
teaching
Vst.-Nr. | Veranstaltungen | Semester |
---|---|---|
D-54062r | Biochemisches Seminar vor Beginn des Semesters in Gruppen als Block | WS 2020/21 |
D-54214 | Seminar: Biochemie (Ribosomengenese) | WS 2020/21 |
D-54215 | Literaturseminar: Funktionelle Zellkernarchitektur | WS 2020/21 |
P-(D)-54071 | Biochemisches Seminar am Ende des Semesters in Gruppen als Block | WS 2020/21 |
P-(D)-54213 | Lehrstuhlseminar: Laufende wissenschaftliche Arbeiten der Biochemie (Ribosomenbiogenese) | WS 2020/21 |
PRA-54063r | Biochemisches Praktikum vor Beginn des Semesters in Gruppen als Block | WS 2020/21 |
PRA-54070 | Biochemisches Praktikum am Ende des Semesters in Gruppen als Block | WS 2020/21 |
PRA-54221 | Forschungspraktikum: Ribosome biogenesis and regulation of transcription | WS 2020/21 |
For further information please visit the university calendar.
Additional teaching
Graduate Research Academy RNA biology - RNA lecture series
“Chemical-biology toolkits to study ribonucleoprotein particles assembly and function”
“Structure probing of RNA and RNPs”
contact
Dr. Sébastien Ferreira-Cerca
Department of Biochemistry III
Biochemistry Center Regensburg
University of Regensburg
Universitaetsstr. 31
Room VKL 5.0.18
D-93053 Regensburg
GERMANY
T: +49-941-943-2539
F: +49-941-943-2474
E: sebastien.ferreira-cerca@ur.de