Susan Baserga, MD, PhD
Research & Publications
Biography
News
Research Summary
Of Yeast and Ribosome Biogenesis: Ribosome biogenesis is a complex process requiring the coordinated expression of rRNA and protein moieties and their assembly in the eukaryotic nucleolus. In order to better understand each aspect of this process, we are using an array of genetic, biochemical, and cell biological techniques in the yeast Saccharomyces cerevisiae. My laboratory focuses on the role of the ribonucleoprotein and protein complexes involved in generating the mature rRNAs.
Specialized Terms: Ribosome biogenesis; RRNA processing; U3 RNP structure and function; RNA helicases; Polymerase I transcription and processing
Extensive Research Description
Study of RNA helicases required for ribosome biogenesis and their cofactors
investigations into the role of ribosome biogenesis in cell cycle regulation
discovery of a subset of SSU processome proteins that are associated with the rDNA and are required for rDNA transcription
identifying
subcomplexes of the SSU processome and deciphering the direct
protein-protein and protein-RNA interactions that mediate their assembly
purification and electron microscopy to visualize pre-ribosomes
characterization of an essential new protein-protein interaction motif found in RNA processing RNPs
developing a method to identify individual proteins in chromatin spreads.
Using innovative proteomics techniques, my laboratory has recently
identified the protein components of a large nucleolar
ribonucleoprotein that is required for processing of the 18S small
subunit rRNA. This RNP, which we termed the SSU processome, is composed
of the U3 snoRNA and 40 proteins. Currently, projects in the lab are
aimed at determining the architecture of this RNP and the functions of
individual proteins in 18S processing. We approach this question from
several perspectives, using genetic and biochemical methods to identify
direct interactions between components, and cryo electron microscopy to
visualize the complex in three dimensions.
Through these studies we
have discovered and characterized several unique protein motifs and
their specific roles in rRNA processing. We have recently discovered
that a subset of the SSU processome proteins are associated with the
rDNA and are required for rDNA transcription. Stemming from this idea,
we are interested in studying the proteins which regulate transcription
of the rDNA by Pol I and initiate the processing of the rRNA. We have
learned that these steps are intimately linked, and endeavor to
describe this complex process in detail. Seventeen putative RNA
helicases have been shown to be required for processing of the small
and large ribosomal subunit RNAs, perhaps by remodeling the rRNA to
allow access to cleavage sites. Ongoing genetic and biochemical studies
in the lab examine the roles of each putative RNA helicase and test its
ability to unwind RNA. Through these projects, we strive to ascertain
how and why the helicases are required at each step in ribosome
biogenesis. Because ribosomes are essential to cell growth via the
production of new proteins, we are studying the role of ribosome
biogenesis in cell cycle regulation.
We have previously shown that rRNA
maturation by the SSU processome is required for cell cycle
progression, indicating that the production of ribosomes has a distinct
influence on the cell cycle. Specifically, we seek to find the
ribosome-regulated trigger that allows the cell to progress through the
cell cycle, grow in size, and divide. Transcription of the rDNA and
processing of the rRNA can be visualized in Miller chromatin spreads,
as shown here. In a, the SSU processome corresponds to the terminal
knobs at the end of each rRNA branching off the rDNA. When components
of the SSU processome are depleted (the U3 snoRNA in b, or the Utp7
protein in c), the knobs are no longer present, due to incomplete
formation of the SSU processome.
Coauthors
Research Interests
Organelle Biogenesis; Genetics; Molecular Biology; Ribonucleoproteins; Radiation Oncology; RNA Helicases; Genes, rRNA
Selected Publications
- Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processingMcCool M, Bryant C, Huang H, Ogawa L, Farley-Barnes K, Sondalle S, Abriola L, Surovtseva Y, Baserga S. Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing RNA Biology 2023, 20: 257-271. PMID: 37246770, PMCID: PMC10228412, DOI: 10.1080/15476286.2023.2217392.
- Human pre-60S assembly factors link rRNA transcription to pre-rRNA processingMcCool M, Buhagiar A, Bryant C, Ogawa L, Abriola L, Surovtseva Y, Baserga S. Human pre-60S assembly factors link rRNA transcription to pre-rRNA processing RNA 2022, 29: rna.079149.122. PMID: 36323459, PMCID: PMC9808572, DOI: 10.1261/rna.079149.122.
- Nucleolar function is regulated by the mitochondrial protein sulfite oxidase (SUOX)McFadden E, Baserga S. Nucleolar function is regulated by the mitochondrial protein sulfite oxidase (SUOX) The FASEB Journal 2022, 36 DOI: 10.1096/fasebj.2022.36.s1.r4250.
- Ribosome Biogenesis and its Role in Cell Growth and Proliferation in the LiverFarley‐Barnes K, Baserga S. Ribosome Biogenesis and its Role in Cell Growth and Proliferation in the Liver 2020, 174-182. DOI: 10.1002/9781119436812.ch15.
- 799 Exome, genome, and cDNA sequencing reveal KDSR mutations cause two forms of ichthyosis and identify retinoids as pathogenesis-directed therapyBoyden L, Vincent N, Zhou J, Hu R, Paller A, Lifton R, Baserga S, Choate K. 799 Exome, genome, and cDNA sequencing reveal KDSR mutations cause two forms of ichthyosis and identify retinoids as pathogenesis-directed therapy Journal Of Investigative Dermatology 2018, 138: s136. DOI: 10.1016/j.jid.2018.03.809.
- High throughput discovery of novel regulators of human ribosome biogenesisBaserga S, Farley‐Barnes K, McCann K, Ogawa L, Merkel J, Surovtseva Y. High throughput discovery of novel regulators of human ribosome biogenesis The FASEB Journal 2018, 32: 526.25-526.25. DOI: 10.1096/fasebj.2018.32.1_supplement.526.25.
- Expression of ribosomopathy genes during Xenopus tropicalis embryogenesisRobson A, Owens ND, Baserga SJ, Khokha MK, Griffin JN. Expression of ribosomopathy genes during Xenopus tropicalis embryogenesis BMC Developmental Biology 2016, 16: 38. PMID: 27784267, PMCID: PMC5081970, DOI: 10.1186/s12861-016-0138-5.
- Nop9 is a PUF-like protein that prevents premature cleavage to correctly process pre-18S rRNAZhang J, McCann KL, Qiu C, Gonzalez LE, Baserga SJ, Hall TM. Nop9 is a PUF-like protein that prevents premature cleavage to correctly process pre-18S rRNA Nature Communications 2016, 7: 13085. PMID: 27725644, PMCID: PMC5062617, DOI: 10.1038/ncomms13085.
- Probing the mechanisms underlying human diseases in making ribosomes.Farley KI, Baserga SJ. Probing the mechanisms underlying human diseases in making ribosomes. Biochemical Society Transactions 2016, 44: 1035-44. PMID: 27528749, PMCID: PMC5360156, DOI: 10.1042/bst20160064.
- The Contributions of the Ribosome Biogenesis Protein Utp5/WDR43 to Craniofacial DevelopmentSondalle SB, Baserga SJ, Yelick PC. The Contributions of the Ribosome Biogenesis Protein Utp5/WDR43 to Craniofacial Development Journal Of Dental Research 2016, 95: 1214-1220. PMID: 27221611, PMCID: PMC5076753, DOI: 10.1177/0022034516651077.
- Box C/D sRNA stem ends act as stabilizing anchors for box C/D di-sRNPsYip WS, Shigematsu H, Taylor DW, Baserga SJ. Box C/D sRNA stem ends act as stabilizing anchors for box C/D di-sRNPs Nucleic Acids Research 2016, 44: 8976-8989. PMID: 27342279, PMCID: PMC5062973, DOI: 10.1093/nar/gkw576.
- The molecular basis for ANE syndrome revealed by the large ribosomal subunit processome interactomeMcCann KL, Teramoto T, Zhang J, Hall T, Baserga SJ. The molecular basis for ANE syndrome revealed by the large ribosomal subunit processome interactome ELife 2016, 5: e16381. PMID: 27077951, PMCID: PMC4859800, DOI: 10.7554/elife.16381.
- A protein interaction map of the LSU processomeMcCann KL, Charette JM, Vincent NG, Baserga SJ. A protein interaction map of the LSU processome Genes & Development 2015, 29: 862-875. PMID: 25877921, PMCID: PMC4403261, DOI: 10.1101/gad.256370.114.
- Determinants of mammalian nucleolar architectureFarley KI, Surovtseva Y, Merkel J, Baserga SJ. Determinants of mammalian nucleolar architecture Chromosoma 2015, 124: 323-331. PMID: 25670395, PMCID: PMC4534358, DOI: 10.1007/s00412-015-0507-z.
- Cryo-Electron Microscopic Study of the Enzymatic Mechanism of the RNA 2'-O-Methyltransferase Box C\D sRNPYip W, Shigematsu H, Taylor D, Wang H, Baserga S. Cryo-Electron Microscopic Study of the Enzymatic Mechanism of the RNA 2'-O-Methyltransferase Box C\D sRNP Microscopy And Microanalysis 2014, 20: 1284-1285. DOI: 10.1017/s1431927614008150.
- Making Ribosomes: Pre-rRNA Transcription and ProcessingMcCann K, Baserga S. Making Ribosomes: Pre-rRNA Transcription and Processing 2014, 217-232. DOI: 10.1007/978-3-319-05687-6_9.
- Discovering the pre‐60S ribosome biogenesis factor interactome (560.7)McCann K, Charette J, Vincent N, Baserga S. Discovering the pre‐60S ribosome biogenesis factor interactome (560.7) The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.560.7.
- The novel zebrafish mutant fantome/wdr43 as a human craniofacial ribosomopathy modelLaBonty M, Zhao C, McCann K, Andreeva V, Baserga S, Yelick P. The novel zebrafish mutant fantome/wdr43 as a human craniofacial ribosomopathy model The FASEB Journal 2013, 27: 319.1-319.1. DOI: 10.1096/fasebj.27.1_supplement.319.1.
- NOL11, implicated in the pathogenesis of North American Indian Childhood Cirrhosis, is required for pre‐rRNA transcription and processingBaserga S, Freed E, Prieto J, McCann K, McStay B. NOL11, implicated in the pathogenesis of North American Indian Childhood Cirrhosis, is required for pre‐rRNA transcription and processing The FASEB Journal 2013, 27: 552.1-552.1. DOI: 10.1096/fasebj.27.1_supplement.552.1.
- The Box C/D sRNP dimeric architecture is conserved across Kingdom ArchaeaBaserga S, Phipps K, Taylor D, Wang H. The Box C/D sRNP dimeric architecture is conserved across Kingdom Archaea The FASEB Journal 2012, 26: 773.2-773.2. DOI: 10.1096/fasebj.26.1_supplement.773.2.
- Small Ribonucleoproteins in Ribosome BiogenesisBleichert F, Baserga S. Small Ribonucleoproteins in Ribosome Biogenesis 2011, 135-156. DOI: 10.1007/978-1-4614-0514-6_7.
- The initial U3 snoRNA:pre‐rRNA base‐pairing interaction required for pre‐18S rRNA folding revealed by in vivo chemical probingBaserga S, Dutca L, Gallagher J. The initial U3 snoRNA:pre‐rRNA base‐pairing interaction required for pre‐18S rRNA folding revealed by in vivo chemical probing The FASEB Journal 2011, 25: 704.1-704.1. DOI: 10.1096/fasebj.25.1_supplement.704.1.
- Electron microscopy reveals that archaeal box C/D sRNPs are di‐sRNPsBleichert F, Gagnon K, Brown B, Maxwell S, Unger V, Baserga S. Electron microscopy reveals that archaeal box C/D sRNPs are di‐sRNPs The FASEB Journal 2009, 23: 661.2-661.2. DOI: 10.1096/fasebj.23.1_supplement.661.2.
- The nucleolar protein Esf2 interacts directly with the DExD/H box RNA helicase, Dbp8, to stimulate ATP hydrolysisGranneman S, Lin C, Champion EA, Nandineni MR, Zorca C, Baserga SJ. The nucleolar protein Esf2 interacts directly with the DExD/H box RNA helicase, Dbp8, to stimulate ATP hydrolysis Nucleic Acids Research 2006, 34: 3189-3199. PMID: 16772403, PMCID: PMC1483223, DOI: 10.1093/nar/gkl419.
- Autoantibody Recognition of Macromolecular Structures and Their SubunitsChampion E, Baserga S. Autoantibody Recognition of Macromolecular Structures and Their Subunits 2005, 379-417. DOI: 10.1002/3527607854.ch17.
- Targeted Destruction of Small, Stable RNAsDunbar D, Baserga S. Targeted Destruction of Small, Stable RNAs 2004, 81-88. DOI: 10.1007/978-1-59259-777-2_6.
- Fibrillarin and Other snoRNP Proteins Are Targets of Autoantibodies in Xenobiotic-Induced AutoimmunityYang J, Baserga S, Turley S, Pollard K. Fibrillarin and Other snoRNP Proteins Are Targets of Autoantibodies in Xenobiotic-Induced Autoimmunity Clinical Immunology 2001, 101: 38-50. PMID: 11580225, DOI: 10.1006/clim.2001.5099.
- An unexpected, conserved element of the U3 snoRNA is required for Mpp10p association.Wormsley S, Samarsky D, Fournier M, Baserga S. An unexpected, conserved element of the U3 snoRNA is required for Mpp10p association. RNA 2001, 7: 904-19. PMID: 11421365, PMCID: PMC1370138, DOI: 10.1017/s1355838201010238.
- A nucleolar protein related to ribosomal protein L7 is required for an early step in large ribosomal subunit biogenesisDunbar D, Dragon F, Lee S, Baserga S. A nucleolar protein related to ribosomal protein L7 is required for an early step in large ribosomal subunit biogenesis Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 13027-13032. PMID: 11087857, PMCID: PMC27172, DOI: 10.1073/pnas.97.24.13027.
- The genes for small nucleolar RNAs in Trypanosoma brucei are organized in clusters and are transcribed as a polycistronic RNADunbar D, Chen A, Wormsley S, Baserga S. The genes for small nucleolar RNAs in Trypanosoma brucei are organized in clusters and are transcribed as a polycistronic RNA Nucleic Acids Research 2000, 28: 2855-2861. PMID: 10908346, PMCID: PMC102681, DOI: 10.1093/nar/28.15.2855.
- Fibrillarin-associated Box C/D Small Nucleolar RNAs inTrypanosoma brucei SEQUENCE CONSERVATION AND IMPLICATIONS FOR 2′-O-RIBOSE METHYLATION OF rRNA*Dunbar D, Wormsley S, Lowe T, Baserga S. Fibrillarin-associated Box C/D Small Nucleolar RNAs inTrypanosoma brucei SEQUENCE CONSERVATION AND IMPLICATIONS FOR 2′-O-RIBOSE METHYLATION OF rRNA* Journal Of Biological Chemistry 2000, 275: 14767-14776. PMID: 10747997, DOI: 10.1074/jbc.m001180200.
- Human Nop5/Nop58 is a component common to the box C/D small nucleolar ribonucleoproteins.Lyman S, Gerace L, Baserga S. Human Nop5/Nop58 is a component common to the box C/D small nucleolar ribonucleoproteins. RNA 1999, 5: 1597-604. PMID: 10606270, PMCID: PMC1369881, DOI: 10.1017/s1355838299991288.
- Imp3p and Imp4p, Two Specific Components of the U3 Small Nucleolar Ribonucleoprotein That Are Essential for Pre-18S rRNA ProcessingLee S, Baserga S. Imp3p and Imp4p, Two Specific Components of the U3 Small Nucleolar Ribonucleoprotein That Are Essential for Pre-18S rRNA Processing Molecular And Cellular Biology 1999, 19: 5441-5452. PMID: 10409734, PMCID: PMC84386, DOI: 10.1128/mcb.19.8.5441.
- M Phase Phosphoprotein 10 Is a Human U3 Small Nucleolar Ribonucleoprotein ComponentWestendorf J, Konstantinov K, Wormsley S, Shu M, Matsumoto-Taniura N, Pirollet F, Klier F, Gerace L, Baserga S. M Phase Phosphoprotein 10 Is a Human U3 Small Nucleolar Ribonucleoprotein Component Molecular Biology Of The Cell 1998, 9: 437-449. PMID: 9450966, PMCID: PMC25272, DOI: 10.1091/mbc.9.2.437.
- The U14 snoRNA is required for 2'-O-methylation of the pre-18S rRNA in Xenopus oocytes.Dunbar D, Baserga S. The U14 snoRNA is required for 2'-O-methylation of the pre-18S rRNA in Xenopus oocytes. RNA 1998, 4: 195-204. PMID: 9570319, PMCID: PMC1369608.
- Functional separation of pre-rRNA processing steps revealed by truncation of the U3 small nucleolar ribonucleoprotein component, Mpp10Lee S, Baserga S. Functional separation of pre-rRNA processing steps revealed by truncation of the U3 small nucleolar ribonucleoprotein component, Mpp10 Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 13536-13541. PMID: 9391061, PMCID: PMC28341, DOI: 10.1073/pnas.94.25.13536.
- Mpp10p, a U3 Small Nucleolar Ribonucleoprotein Component Required for Pre-18S rRNA Processing in YeastDunbar D, Wormsley S, Agentis T, Baserga S. Mpp10p, a U3 Small Nucleolar Ribonucleoprotein Component Required for Pre-18S rRNA Processing in Yeast Molecular And Cellular Biology 1997, 17: 5803-5812. PMID: 9315638, PMCID: PMC232428, DOI: 10.1128/mcb.17.10.5803.
- Mpp10p, a new protein component of the U3 snoRNP required for processing of 18S rRNA precursors.Baserga S, Agentis T, Wormsley S, Dunbar D, Lee S. Mpp10p, a new protein component of the U3 snoRNP required for processing of 18S rRNA precursors. Nucleic Acids Symposium Series 1997, 64-7. PMID: 9478208.
- The U18 snRNA is not essential for pre-rRNA processing in Xenopus laevis.Dunbar D, Ware V, Baserga S. The U18 snRNA is not essential for pre-rRNA processing in Xenopus laevis. RNA 1996, 2: 324-33. PMID: 8634913, PMCID: PMC1369375.
- Ella Clay Wakeman: Yale School of Medicine, 1921.Baserga S, Calhoun D, Calhoun L. Ella Clay Wakeman: Yale School of Medicine, 1921. The Yale Journal Of Biology And Medicine 1995, 68: 171-90. PMID: 8903041, PMCID: PMC2588935.
- Distinct molecular signals for nuclear import of the nucleolar snRNA, U3.Baserga S, Gilmore-Hebert M, Yang X. Distinct molecular signals for nuclear import of the nucleolar snRNA, U3. Genes & Development 1992, 6: 1120-1130. PMID: 1592260, DOI: 10.1101/gad.6.6.1120.
- Beta-globin nonsense mutation: deficient accumulation of mRNA occurs despite normal cytoplasmic stability.Baserga S, Benz E. Beta-globin nonsense mutation: deficient accumulation of mRNA occurs despite normal cytoplasmic stability. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 2935-2939. PMID: 1557399, PMCID: PMC48778, DOI: 10.1073/pnas.89.7.2935.
- Three pseudogenes for human U13 snRNA belong to class IIIBaserga S, Yang X, Steitz J. Three pseudogenes for human U13 snRNA belong to class III Gene 1991, 107: 347-348. PMID: 1748306, DOI: 10.1016/0378-1119(91)90340-h.
- Metabolism of Non‐Translatable Globin mRNAs Arising from Premature Translation Termination CodonsMAGNUS T, BASERGA S, STOLLE C, TAKESHITA K, BENZ E. Metabolism of Non‐Translatable Globin mRNAs Arising from Premature Translation Termination Codons Annals Of The New York Academy Of Sciences 1990, 612: 55-66. PMID: 2291574, DOI: 10.1111/j.1749-6632.1990.tb24290.x.
- Nonsense mutations in the human beta-globin gene affect mRNA metabolism.Baserga S, Benz E. Nonsense mutations in the human beta-globin gene affect mRNA metabolism. Proceedings Of The National Academy Of Sciences Of The United States Of America 1988, 85: 2056-2060. PMID: 3353367, PMCID: PMC279927, DOI: 10.1073/pnas.85.7.2056.
- Detecting small mutations in expressed genes by a combination of S1 nuclease and RNase AAtweh G, Baserga S, Brickner H. Detecting small mutations in expressed genes by a combination of S1 nuclease and RNase A Nucleic Acids Research 1988, 16: 8709-8709. PMID: 2843823, PMCID: PMC338588, DOI: 10.1093/nar/16.17.8709.
- Polyadenylation of a human mitochondrial ribosomal RNA transcript detected by molecular cloningBaserga S, Linnenbach A, Malcolm S, Ghosh P, Malcolm A, Takeshita K, Forget B, Benz E. Polyadenylation of a human mitochondrial ribosomal RNA transcript detected by molecular cloning Gene 1985, 35: 305-312. PMID: 4043734, DOI: 10.1016/0378-1119(85)90009-5.