Katrin Karbstein

Katrin Karbstein, Ph.D.

Professor

Department: SR-IS&CB-KARBSTEIN LAB
Business Phone: (561) 228-3210
Business Email: katrin.karbstein@ufl.edu

About Katrin Karbstein

Related Links:
Additional Positions:
Professor, Integrative Structural and Computational Biology
2020 – Current · UF Scripps Biomedical Research
Associate Professor, Integrative Structural and Computational Biology (ISCB)
2017 – 2019 · Scripps Research
Associate Professor (Joint Appointment), Cell and Molecular Biology (CMB)
2013 – 2017 · Scripps Research
Associate Professor, Cancer Biology
2012 – 2017 · Scripps Research
Assistant Professor, Cancer Biology
2010 – 2012 · Scripps Research

Accomplishments

HHMI Faculty Scholar Award
2016 · Howard Hughes Medical Institute
NSF CAREER Award
2009 ·
Seyhan Ege Professorship
2009 · University of Michigan, Department of Chemistry
Biological Sciences Scholar Award
2006 · University of Michigan

Research Profile

Mechanisms of Ribosome Assembly, Quality Control and the Molecular Basis for Ribosome-Associated Diseases (Ribosomopathies)

We study the mechanisms that (i) promote correct ribosome assembly, (ii) allow for the quality control of assembly intermediates and their degradation, and (iii) dissect the consequences of their bypass when misassembled ribosomes escape to the translating pool.

Ribosomes are the largest, most abundant and most conserved RNA-protein complexes, catalyzing protein synthesis in all cells. In doing so, they must interpret the information contained in the mRNA to produce the right amount of the correct protein. In addition, ribosomes are also central to the maintenance of mRNA quality control. Thus, misassembled ribosomes can affect the sequence and abundance of proteins and mRNAs, thereby globally disrupting protein homeostasis. As a result, a number of diseases arise from defects in ribosome assembly.

Ribosome assembly involves the coordinated transcription, modification and processing of ribosomal RNA (rRNA), integrated with the binding of ribosomal proteins (RPs), and the subsequent folding of the rRNA. In eukaryotes, this process involves a machinery of over 200 assembly factors (AFs), and is initiated co-transcriptionally in the nucleolus, resulting in the formation of assembly intermediates that are partially matured and contain most RPs. These intermediates are exported into the cytoplasm, where final maturation takes place. Importantly, these last maturation events are integrated with quality control steps, thereby ensuring only fully and correctly assembled ribosomes enter the translating pool.

A number of diseases result from the escape of misassembled ribosomes into the translating pool. These can arise either from point mutations in AFs, or from RP haploinsufficiency, which leads to reduced ribosome concentrations, as well as the accumulation of ribosomes lacking the insufficient (and sometimes adjacent) proteins. These diseases share a predisposition to specific cancers. Furthermore, ribosomes from cancer cells lose the stoichiometry of their component proteins, which is associated with a poor prognosis, and normally suppressed by p53. Together, these data demonstrate the importance of (i) ensuring that all RPs are correctly incorporated into ribosomes, and of (ii) quality control mechanisms to identify and ultimately remove incompletely or incorrectly assembled intermediates. Furthermore, these diseases also motivate (iii) a better understanding of how misassembled ribosomes and dysregulated ribosome numbers lead to cancer. We study these key questions in a combination of biochemical, genetic, and genomic experiments, taking advantage of the yeast system, and moving into human cells if necessary. http://www.scripps.edu/karbstein

Open Researcher and Contributor ID (ORCID)

0000-0002-4034-1331

Publications

2022
The chaperone Tsr2 regulates Rps26 release and reincorporation from mature ribosomes to enable a reversible, ribosome-mediated response to stress
Science Advances. 8(8) [DOI] 10.1126/sciadv.abl4386. [PMID] 35213229.
2022
The modifying enzyme Tsr3 establishes the hierarchy of Rio kinase binding in 40S ribosome assembly
RNA. 28(4):568-582 [DOI] 10.1261/rna.078994.121. [PMID] 35031584.
2022
The promises and pitfalls of specialized ribosomes.
Molecular cell. 82(12):2179-2184 [DOI] 10.1016/j.molcel.2022.05.035. [PMID] 35714581.
2022
Using DMS-MaPseq to uncover the roles of DEAD-box proteins in ribosome assembly.
Methods (San Diego, Calif.). 204:249-257 [DOI] 10.1016/j.ymeth.2022.05.001. [PMID] 35550176.
2021
An open interface in the pre-80S ribosome coordinated by ribosome assembly factors Tsr1 and Dim1 enables temporal regulation of Fap7
RNA. 27(2):221-233 [DOI] 10.1261/rna.077610.120. [PMID] 33219089.
2021
Assembly factors chaperone ribosomal RNA folding by isolating helical junctions that are prone to misfolding
Proceedings of the National Academy of Sciences. 118(25) [DOI] 10.1073/pnas.2101164118. [PMID] 34135123.
2020
Correction: A kinase-dependent checkpoint prevents escape of immature ribosomes into the translating pool.
PLoS biology. 18(10) [DOI] 10.1371/journal.pbio.3000960. [PMID] 33048931.
2020
Faculty Opinions recommendation of Transcription increases the cooperativity of ribonucleoprotein assembly.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. [DOI] 10.3410/f.736952961.793571081.
2020
Faculty Opinions recommendation of Transient Protein-RNA Interactions Guide Nascent Ribosomal RNA Folding.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. [DOI] 10.3410/f.736952966.793571417.
2020
Quality control of 40S ribosome head assembly ensures scanning competence
Journal of Cell Biology. 219(11) [DOI] 10.1083/jcb.202004161. [PMID] 33007085.
2019
A kinase-dependent checkpoint prevents escape of immature ribosomes into the translating pool
PLOS Biology. 17(12) [DOI] 10.1371/journal.pbio.3000329. [PMID] 31834877.
2019
Does functional specialization of ribosomes really exist?
RNA (New York, N.Y.). 25(5):521-538 [DOI] 10.1261/rna.069823.118. [PMID] 30733326.
2019
Faculty Opinions recommendation of Introns are mediators of cell response to starvation.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. [DOI] 10.3410/f.734863374.793561561.
2019
Faculty Opinions recommendation of mRNA structure determines modification by pseudouridine synthase 1.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. [DOI] 10.3410/f.736539008.793568372.
2019
Mitochondria teach ribosome assembly.
Science (New York, N.Y.). 365(6458):1077-1078 [DOI] 10.1126/science.aay7771. [PMID] 31515371.
2019
Psp2, a novel regulator of autophagy that promotes autophagy-related protein translation.
Cell research. 29(12):994-1008 [DOI] 10.1038/s41422-019-0246-4. [PMID] 31666677.
2019
Rrp5 establishes a checkpoint for 60S assembly during 40S maturation
RNA. 25(9):1164-1176 [DOI] 10.1261/rna.071225.119. [PMID] 31217256.
2018
Faculty Opinions recommendation of AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. [DOI] 10.3410/f.732405346.793541369.
2018
Faculty Opinions recommendation of Preribosomes escaping from the nucleus are caught during translation by cytoplasmic quality control.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. [DOI] 10.3410/f.732052512.793541368.
2018
Faculty Opinions recommendation of Ribosome Collision Is Critical for Quality Control during No-Go Decay.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. [DOI] 10.3410/f.731312455.793542570.
2018
Faculty Opinions recommendation of Spliceosome profiling visualizes operations of a dynamic RNP at nucleotide resolution.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. [DOI] 10.3410/f.733159899.793551573.
2018
Faculty Opinions recommendation of The helicase Ded1p controls use of near-cognate translation initiation codons in 5′ UTRs.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. [DOI] 10.3410/f.733524062.793548134.
2018
Responsible Peer Review.
ACS chemical biology. 13(12):3217-3218 [DOI] 10.1021/acschembio.8b01035. [PMID] 30993984.
2018
Ribosome biogenesis factor Ltv1 chaperones the assembly of the small subunit head
Journal of Cell Biology. 217(12):4141-4154 [DOI] 10.1083/jcb.201804163. [PMID] 30348748.
2018
Translational Reprogramming Provides a Blueprint for Cellular Adaptation.
Cell chemical biology. 25(11):1372-1379.e3 [DOI] 10.1016/j.chembiol.2018.08.003. [PMID] 30174311.
2017
Rps26 directs mRNA-specific translation by recognition of Kozak sequence elements
Nature Structural & Molecular Biology. 24(9):700-707 [DOI] 10.1038/nsmb.3442. [PMID] 28759050.
2017
Structural Heterogeneity in Pre-40S Ribosomes.
Structure (London, England : 1993). 25(2):329-340 [DOI] 10.1016/j.str.2016.12.011. [PMID] 28111018.
2017
The ATPase Fap7 Tests the Ability to Carry Out Translocation-like Conformational Changes and Releases Dim1 during 40S Ribosome Maturation.
Molecular cell. 68(6) [DOI] 10.1016/j.molcel.2017.12.001. [PMID] 29272706.
2017
The ATPase Fap7 Tests the Ability to Carry Out Translocation-like Conformational Changes and Releases Dim1 during 40S Ribosome Maturation.
Molecular cell. 67(6):990-1000.e3 [DOI] 10.1016/j.molcel.2017.08.007. [PMID] 28890337.
2016
The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation.
PLoS biology. 14(6) [DOI] 10.1371/journal.pbio.1002480. [PMID] 27280440.
2015
Functions of ribosomal proteins in assembly of eukaryotic ribosomes in vivo.
Annual review of biochemistry. 84:93-129 [DOI] 10.1146/annurev-biochem-060614-033917. [PMID] 25706898.
2015
Hrr25/CK1δ-directed release of Ltv1 from pre-40S ribosomes is necessary for ribosome assembly and cell growth.
The Journal of cell biology. 208(6):745-59 [DOI] 10.1083/jcb.201409056. [PMID] 25778921.
2015
Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade.
Cell reports. 10(5):684-693 [DOI] 10.1016/j.celrep.2015.01.014. [PMID] 25660019.
2015
What will the future hold: RNP quality control and degradation.
RNA (New York, N.Y.). 21(4):657-8 [DOI] 10.1261/rna.050658.115. [PMID] 25780179.
2013
Cofactor-dependent specificity of a DEAD-box protein.
Proceedings of the National Academy of Sciences of the United States of America. 110(29):E2668-76 [DOI] 10.1073/pnas.1302577110. [PMID] 23630256.
2013
Quality control mechanisms during ribosome maturation.
Trends in cell biology. 23(5):242-50 [DOI] 10.1016/j.tcb.2013.01.004. [PMID] 23375955.
2012
A translation-like cycle is a quality control checkpoint for maturing 40S ribosome subunits.
Cell. 150(1):111-21 [DOI] 10.1016/j.cell.2012.04.044. [PMID] 22770215.
2012
Analysis of cofactor effects on RNA helicases.
Methods in enzymology. 511:213-37 [DOI] 10.1016/B978-0-12-396546-2.00010-3. [PMID] 22713322.
2011
An RNA conformational switch regulates pre-18S rRNA cleavage.
Journal of molecular biology. 405(1):3-17 [DOI] 10.1016/j.jmb.2010.09.064. [PMID] 20934433.
2011
Inside the 40S ribosome assembly machinery.
Current opinion in chemical biology. 15(5):657-63 [DOI] 10.1016/j.cbpa.2011.07.023. [PMID] 21862385.
2011
Protein-protein interactions within late pre-40S ribosomes.
PloS one. 6(1) [DOI] 10.1371/journal.pone.0016194. [PMID] 21283762.
2011
Rcl1 protein, a novel nuclease for 18 S ribosomal RNA production.
The Journal of biological chemistry. 286(39):34082-7 [DOI] 10.1074/jbc.M111.268649. [PMID] 21849504.
2011
Ribosome assembly factors prevent premature translation initiation by 40S assembly intermediates.
Science (New York, N.Y.). 333(6048):1449-53 [DOI] 10.1126/science.1208245. [PMID] 21835981.
2011
Roles of Dim2 in ribosome assembly.
The Journal of biological chemistry. 286(4):2578-86 [DOI] 10.1074/jbc.M110.191494. [PMID] 21075849.
2011
The roles of S1 RNA-binding domains in Rrp5’s interactions with pre-rRNA.
RNA (New York, N.Y.). 17(3):512-21 [DOI] 10.1261/rna.2458811. [PMID] 21233221.
2010
Chaperoning ribosome assembly.
The Journal of cell biology. 189(1):11-2 [DOI] 10.1083/jcb.201002102. [PMID] 20368615.
2009
Nob1 binds the single-stranded cleavage site D at the 3′-end of 18S rRNA with its PIN domain.
Proceedings of the National Academy of Sciences of the United States of America. 106(34):14259-64 [DOI] 10.1073/pnas.0905403106. [PMID] 19706509.
2009
Powering through ribosome assembly.
RNA (New York, N.Y.). 15(12):2083-104 [DOI] 10.1261/rna.1792109. [PMID] 19850913.
2007
Closing the gap between interdisciplinary research and disciplinary teaching.
ACS chemical biology. 2(8):518-20 [PMID] 17708666.
2007
Probing the role of a secondary structure element at the 5′- and 3′-splice sites in group I intron self-splicing: the tetrahymena L-16 ScaI ribozyme reveals a new role of the G.U pair in self-splicing.
Biochemistry. 46(16):4861-75 [PMID] 17385892.
2007
RNA takes center stage.
Biopolymers. 87(5-6):275-8 [PMID] 17688253.
2007
Role of GTPases in ribosome assembly.
Biopolymers. 87(1):1-11 [PMID] 17514744.
2006
GTP-dependent formation of a ribonucleoprotein subcomplex required for ribosome biogenesis.
Journal of molecular biology. 356(2):432-43 [PMID] 16376378.
2005
An essential GTPase promotes assembly of preribosomal RNA processing complexes.
Molecular cell. 20(4):633-43 [PMID] 16307926.
2004
A base triple in the Tetrahymena group I core affects the reaction equilibrium via a threshold effect.
RNA (New York, N.Y.). 10(11):1730-9 [PMID] 15496521.
2004
RNA: primed for packing?
Chemistry & biology. 11(2):149-51 [PMID] 15123272.
2003
Extraordinarily slow binding of guanosine to the Tetrahymena group I ribozyme: implications for RNA preorganization and function.
Proceedings of the National Academy of Sciences of the United States of America. 100(5):2300-5 [PMID] 12591943.
2002
Probing the Tetrahymena group I ribozyme reaction in both directions.
Biochemistry. 41(37):11171-83 [PMID] 12220182.
1999
Identification of the hammerhead ribozyme metal ion binding site responsible for rescue of the deleterious effect of a cleavage site phosphorothioate.
Biochemistry. 38(43):14363-78 [PMID] 10572011.
A kinase-dependent checkpoint prevents escape of immature ribosomes into the translating pool
. [DOI] 10.1101/656942.
Assembly factors chaperone rRNA folding by isolating helical junctions that are prone to misfolding
. [DOI] 10.1101/2020.09.29.318998.
Blocking a dead-end assembly pathway creates a point of regulation for the DEAD-box ATPase Has1 and prevents platform misassembly
. [DOI] 10.1101/2021.09.06.459192.
Chaperone-Directed Ribosome Repair after Oxidative Damage
. [DOI] 10.1101/2022.07.28.501866.
The chaperone Tsr2 regulates Rps26 release and reincorporation from mature ribosomes to enable a reversible, ribosome-mediated response to stress
. [DOI] 10.1101/2021.04.05.438496.
The kinase Rio1 and a ribosome collision-dependent decay pathway survey the integrity of 18S rRNA cleavage
. [DOI] 10.1101/2022.07.29.501969.
The modifying enzyme Tsr3 establishes the hierarchy of Rio kinase activity in 40S ribosome assembly
. [DOI] 10.1101/2021.09.28.462141.

Grants

Apr 2022 ACTIVE
Dissecting the Mechanisms of Regulation and Quality Control in Ribosome Assembly and the Consequences of their Failure
Role: Principal Investigator
Funding: NATL INST OF HLTH NIGMS
Apr 2022 ACTIVE
2016 Faculty Scholars Competition
Role: Principal Investigator
Funding: HUGHES MEDICAL INST, HOWARD
Apr 2022 – Jul 2022
Unraveling the mechanism by which Rps26-deficient ribosomes form to support the stress response
Role: Principal Investigator
Funding: NATL INST OF HLTH NIGMS
Apr 2022 ACTIVE
REU Site: SURFing the Interface between Chemistry and Biology
Role: Principal Investigator
Funding: NATL SCIENCE FOU

Education

Ph.D. in Biochemistry
2003 · Stanford University
Diploma in Biochemistry
1998 · Witten/Herdecke University
Diploma in Chemistry
1995 · Ruhr University Bochum

Contact Details

Phones:
Business:
(561) 228-3210
Emails:
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Location C241
130 SCRIPPS WAY BLDG 2C2
JUPITER FL 33458