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Groupleader: Jirka Peschek
Jirka Peschek
RNA Processing and Repair
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Research
The cellular pool of ribonucleic acids (RNAs) is immensely diverse and complex. During their biosynthesis, RNA molecules undergo a vast number of co- and posttranscriptional processing and modification steps, which require dedicated enzyme machinery.
tRNA Splicing
One unique example of RNA processing is non-conventional splicing of RNAs, which is an essential step during transfer RNA (tRNA) maturation. tRNAs are transcribed as precursor transcripts (pre-tRNA) and are subjected to multiple posttranscriptional processing events before they can fulfil their function. Intron-containing pre-tRNAs undergo non-conventional splicing—a cytosolic, enzyme-catalysed processing reaction. The splicing of pre-tRNAs occurs in two steps: The intron is first excised by a splicing endonuclease and the resulting tRNA exon halves are ligated by tRNA ligase to form a fully matured functional tRNA. Because eukaryotic tRNA introns disrupt the anticodon stem-loop structure, the removal of these introns is an essential process.
In our lab, we aim to comprehend the structure and function of the eukaryotic tRNA splicing machinery. The mechanistic and structural insights will provide a comprehensive picture of how tRNA splicing enzymes function in the cell.
RNA Repair
While there is a substantial understanding for the various RNA maturation and degradation pathways, much less attention has been given to RNA repair and quality control. RNA can be subjected to damage through non-enzymatic hydrolysis or the action of endonucleases. These RNA cleavage events can be “sealed” by RNA ligases, which catalyse the ligation via phosphodiester bonds. We aim to uncover new RNA repair and quality control pathways based on these enzymes.
Our Approach
Using an interdisciplinary approach from protein and RNA biochemistry to structural biology and yeast genetics, we analyse the machinery and mechanisms that maintain RNA integrity. We often start by in vitro reconstitution of enzyme complexes, to determine their structure-function relationships. Once we purified protein, we study it using x-ray crystallography, cryo-electron microscopy (cryo-EM) as well as biophysical and biochemical methods. We explore the cellular role of RNA processing enzymes in the yeast Saccharomyces cerevisiae and mammalian cells.
The lab in April 2023
Lab Members
Ege Çigirgan
PhD student
PhD student
Lab:Room 421
/ Phone: +49 6221 54-4235
Mail:ege.cigirgan@bzh.uni-heidelberg.de
Janina Lara Gerber
PhD student
PhD student
Lab:Room 421
/ Phone: +49 6221 54-4235
Mail:janina.gerber@bzh.uni-heidelberg.de
Sandra Köhler
PhD student
PhD student
Lab:Room 421
/ Phone: +49 6221 54-4235
Mail:sandra.koehler@bzh.uni-heidelberg.de
Alexander Niklas Wirth
PhD student
PhD student
Lab:Room 421
/ Phone: +49 6221 54-4235
Mail:alexander.wirth@bzh.uni-heidelberg.de
Publications
Selected Publications
Gerber JL, Morales Guzmán SI, Worf L, Hubbe P, Kopp J, Peschek J (2023) Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease. bioRxiv. https://doi.org/10.1101/2023.03.30.534986
Li W*, Crotty K*, Garrido Ruiz D, Voorhies M, Rivera C, Sil A, Mullins RD, Jacobson MP, Peschek J§, Walter P§ (2021) Protomer alignment modulates specificity of RNA substrate recognition by Ire1. eLife 10:e67425
Peschek J§ & Walter P§ (2019) tRNA ligase structure reveals kinetic competition between non-conventional mRNA splicing and mRNA decay. eLife 8:e44199.
Li W, Okreglak V, Peschek J, Kimmig P, Zubradt M, Weissman JS, Walter P (2018) Engineering ER-stress dependent non-conventional mRNA splicing. eLife 7: e35388.
Peschek J*, Acosta-Alvear D*, Mendez AS, Walter P (2015) A conformational RNA zipper promotes intron ejection during non-conventional XBP1 mRNA splicing. EMBO Rep. 16(12):1688-98.
Mainz A, Peschek J, Stavropoulou M, Back KC, Bardiaux B, Asami S, Prade E, Peters C, Weinkauf S, Buchner J, Reif B (2015) The chaperone αB-crystallin uses different interfaces to capture an amorphous and an amyloid client. Nat Struct Mol Biol. 22(11):898-905.
Feige MJ, Gräwert MA, Marcinowski M, Hennig J, Behnke J, Ausländer D, Herold EM, Peschek J, Castro CD, Flajnik M, Hendershot LM, Sattler M, Groll M, Buchner J (2014) The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins. PNAS 111(22):8155-60.
Peschek J, Braun N, Rohrberg J, Back KC, Kriehuber T, Kastenmüller A, Weinkauf S, Buchner J (2013) Regulated structural transitions unleash the chaperone activity of αB-crystallin. PNAS 110(40):E3780-9.
Müller R, Gräwert MA, Kern T, Madl T, Peschek J, Sattler M, Groll M, Buchner J (2013) High-resolution structures of the IgM Fc domains reveal principles of its hexamer formation. PNAS 110(25):10183-8.
Drazic A, Miura H, Peschek J, Le Y, Bach NC, Kriehuber T, Winter J (2013) Methionine oxidation activates a transcription factor in response to oxidative stress. PNAS 110(23):9493-8.
Braun N, Zacharias M, Peschek J, Kastenmüller A, Zou J, Hanzlik M, Haslbeck M, Rappsilber J, Buchner J, Weinkauf S (2011) Multiple molecular architectures of the eye lens chaperone αB-crystallin elucidated by a triple hybrid approach. PNAS 108(51):20491-20496.
Peschek J*, Braun N*, Franzmann TM*, Georgalis Y, Haslbeck M, Weinkauf S, Buchner J (2009) The eye lens chaperone α-crystallin forms defined globular assemblies. PNAS 106(32):13272-13277.
Reviews and Method Papers
JL Gerber*, S Köhler*, J Peschek (2022) Eukaryotic tRNA splicing–one goal, two strategies, many players. Biological Chemistry 403(8-9): 765-778.
Peschek J (2021) Mechanismen des nicht konventionellen RNA-Spleißens. BIOspektrum 27(3): 233–236
Karagöz GE, Peschek J, Walter P, Acosta-Alvear D (2019) In vitro RNA Cleavage Assays to Characterize IRE1-dependent RNA Decay. Bio-protocol 9(14):e3307.
Haslbeck M, Peschek, Buchner J, Weinkauf S (2016) Structure and function of α-crystallins: Traversing from in vitro to in vivo. Biochim Biophys Acta 1860(1 Pt B):149-66. [Review]
Complete List of Publications
https://orcid.org/0000-0001-8158-9301
CV
Academic Training and Positions
| Since 2020 | Emmy Noether Group Leader, Biochemistry Center, Heidelberg University |
| 2013-2020 | Postdoc with Peter Walter, UCSF, San Francisco, USA |
| 2012 | PhD (Biochemistry), Technical University of Munich |
| 2008-2012 | PhD student with Johannes Buchner, Technical University of Munich |
Awards and Honours
| 2020 | Emmy Noether Fellowship |
| 2014-2017 | Human Frontier Science Program Fellow |
| 2017 | The Protein Society, Hans Neurath Outstanding Promise Travel Award |
| 2009-2011 | Studienstiftung des deutschen Volkes, Doctoral Scholarship |
Funding
CRC/Transregio 319 - RMaP: RNA Modification and Processing
Open Positions
We are permanently looking for highly motivated Bachelor/Master/Diploma students to join our team.
If interested, please send your application including a CV, a letter of motivation and possible references to: jirka.peschek@bzh.uni-heidelberg.de
For students of Biochemistry, Molecular Biotechnology and Molecular Biosciences: If you are interested in a lab rotation and want to learn more about ongoing projects in the lab, please send us an email.
We are currently hiring a postdoctoral researcher and a PhD student:
If interested, please send your application including a CV, a letter of motivation and possible references to: jirka.peschek@bzh.uni-heidelberg.de
For students of Biochemistry, Molecular Biotechnology and Molecular Biosciences: If you are interested in a lab rotation and want to learn more about ongoing projects in the lab, please send us an email.
We are currently hiring a postdoctoral researcher and a PhD student:
Lab Pictures
The lab in March 2022
1st lab anniversary (October 2021)
The lab in April 2021
Contact
Office No: 402
Lab No: 421
Biochemie-Zentrum
der Universität Heidelberg (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
der Universität Heidelberg (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
Office:
+49 6221 54-4151 Lab:
+49 6221 54-4235 Fax:
+49 6221 54-4369 E-Mail:
jirka.peschek@bzh.uni-heidelberg.de