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Elizabeth Grayhack, Ph.D.

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Elizabeth Grayhack, Ph.D.

About Me
Credentials
Research
Publications

About Me

Faculty Appointments

Associate Professor - Department of Biochemistry and Biophysics (SMD)

Credentials

Education

PhD | Cornell University. Biology. 1981

BA | Lawrence University. Chemistry. 1974

Research

Translation of the genetic code from triplet codons in mRNAs into the amino acids in proteins determines the protein composition in the cell. The translation process influences the amount of each protein, the errors within each protein, as well as programmed deviations that affect the protein sequence. Although accurate and efficient translation of mRNA into proteins is crucially important for the cell, there are substantial differences in translation caused by the choice of synonymous codons used to encode a polypeptide. Synonymous codons specify insertion of the identical amino acid, but differ from each other in the amounts of tRNA available to decode the codon as well as the need for wobble base pairing between the codon and the anticodon of the tRNA.

The goal of research in the Grayhack laboratory is to define the rules and mechanisms by which specific arrangements of codons impair translation in the yeast Saccharomyces cerevisiae, and to identify regulatory models dictated by codon usage in the yeast genome. Although codon use has been implicated as a determinant of expression levels, neither the identity, nor the defining characteristics of codons that impair expression are known. We demonstrated that translation of CGA codon pairs is remarkably inefficient due to wobble decoding, which implicated interactions between sites in the ribosome and the ribosome decoding process as mediators of translation efficiency. We are currently examining the mechanisms by which CGA codon pairs modulate translation and defining novel codon combinations that reduce translation efficiency.

Publications

Journal Articles

Frameshifting at collided ribosomes is modulated by elongation factor eEF3 and by integrated stress response regulators Gcn1 and Gcn20.

Houston L, Platten EM, Connelly SM, Wang J, Grayhack EJ

RNA.. 2022 March 28 (3):320-339. Epub 12/16/2021.

Conservation of location of several specific inhibitory codon pairs in the Saccharomyces sensu stricto yeasts reveals translational selection.

Ghoneim DH, Zhang X, Brule CE, Mathews DH, Grayhack EJ

Nucleic acids research.. 2019 February 2047 (3):1164-1177. Epub 1900 01 01.

Multi-protein bridging factor 1(Mbf1), Rps3 and Asc1 prevent stalled ribosomes from frameshifting.

Wang J, Zhou J, Yang Q, Grayhack EJ

eLife.. 2018 November 227 Epub 11/22/2018.

The analysis of translational mechanisms that modulate gene expression.

Coller J, Grayhack EJ

Methods : a companion to Methods in enzymology.. 2018 March 15137 :1-2. Epub 1900 01 01.

Synonymous Codons: Choose Wisely for Expression.

Brule CE, Grayhack EJ

Trends in genetics : TIG.. 2017 April 33 (4):283-297. Epub 03/12/2017.

A genome wide dosage suppressor network reveals genomic robustness.

Patra B, Kon Y, Yadav G, Sevold AW, Frumkin JP, Vallabhajosyula RR, Hintze A, Østman B, Schossau J, Bhan A, Marzolf B, Tamashiro JK, Kaur A, Baliga NS, Grayhack EJ, Adami C, Galas DJ, Raval A, Phizicky EM, Ray A

Nucleic acids research.. 2017 January 945 (1):255-270. Epub 11/29/2016.

Adjacent Codons Act in Concert to Modulate Translation Efficiency in Yeast.

Gamble CE, Brule CE, Dean KM, Fields S, Grayhack EJ

Cell.. 2016 July 28166 (3):679-690. Epub 06/30/2016.

RNA-ID, a Powerful Tool for Identifying and Characterizing Regulatory Sequences.

Brule CE, Dean KM, Grayhack EJ

Methods in enzymology.. 2016 572 :237-53. Epub 03/11/2016.

Functional profiling in Streptococcus mutans: construction and examination of a genomic collection of gene deletion mutants.

Quivey RG, Grayhack EJ, Faustoferri RC, Hubbard CJ, Baldeck JD, Wolf AS, MacGilvray ME, Rosalen PL, Scott-Anne K, Santiago B, Gopal S, Payne J, Marquis RE

Molecular oral microbiology.. 2015 December 30 (6):474-95. Epub 06/19/2015.

Asc1, homolog of human RACK1, prevents frameshifting in yeast by ribosomes stalled at CGA codon repeats.

Wolf AS, Grayhack EJ

RNA.. 2015 May 21 (5):935-45. Epub 03/19/2015.

Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis.

Guy MP, Young DL, Payea MJ, Zhang X, Kon Y, Dean KM, Grayhack EJ, Mathews DH, Fields S, Phizicky EM

Genes & development.. 2014 August 128 (15):1721-32. Epub 1900 01 01.

Translation of CGA codon repeats in yeast involves quality control components and ribosomal protein L1.

Letzring DP, Wolf AS, Brule CE, Grayhack EJ

RNA.. 2013 September 19 (9):1208-17. Epub 07/03/2013.

The structure of yeast glutaminyl-tRNA synthetase and modeling of its interaction with tRNA.

Grant TD, Luft JR, Wolfley JR, Snell ME, Tsuruta H, Corretore S, Quartley E, Phizicky EM, Grayhack EJ, Snell EH

Journal of molecular biology.. 2013 July 24425 (14):2480-93. Epub 04/10/2013.

RNA-ID, a highly sensitive and robust method to identify cis-regulatory sequences using superfolder GFP and a fluorescence-based assay.

Dean KM, Grayhack EJ

RNA.. 2012 December 18 (12):2335-44. Epub 10/24/2012.

Structural conservation of an ancient tRNA sensor in eukaryotic glutaminyl-tRNA synthetase.

Grant TD, Snell EH, Luft JR, Quartley E, Corretore S, Wolfley JR, Elizabeth Snell M, Hadd A, Perona JJ, Phizicky EM, Grayhack EJ

Nucleic acids research.. 2012 April 40 (8):3723-31. Epub 12/17/2011.

Control of translation efficiency in yeast by codon-anticodon interactions.

Letzring DP, Dean KM, Grayhack EJ

RNA.. 2010 December 16 (12):2516-28. Epub 10/22/2010.

Heterologous expression of L. major proteins in S. cerevisiae: a test of solubility, purity, and gene recoding.

Quartley E, Alexandrov A, Mikucki M, Buckner FS, Hol WG, Detitta GT, Phizicky EM, Grayhack EJ

Journal of structural and functional genomics. 2009 September 10 (3):233-47. Epub 08/22/2009.

Degradation of several hypomodified mature tRNA species in Saccharomyces cerevisiae is mediated by Met22 and the 5'-3' exonucleases Rat1 and Xrn1.

Chernyakov I, Whipple JM, Kotelawala L, Grayhack EJ, Phizicky EM

Genes & development.. 2008 May 1522 (10):1369-80. Epub 04/28/2008.

Identification of yeast tRNA Um(44) 2'-O-methyltransferase (Trm44) and demonstration of a Trm44 role in sustaining levels of specific tRNA(Ser) species.

Kotelawala L, Grayhack EJ, Phizicky EM

RNA.. 2008 January 14 (1):158-69. Epub 11/19/2007.

The use of Saccharomyces cerevisiae proteomic libraries to identify RNA-modifying proteins.

Jackman JE, Grayhack EJ, Phizicky EM

Methods in molecular biology.. 2008 488 :383-93. Epub 1900 01 01.

Chapter 11. Identification and analysis of tRNAs that are degraded in Saccharomyces cerevisiae due to lack of modifications.

Chernyakov I, Baker MA, Grayhack EJ, Phizicky EM

Methods in enzymology.. 2008 449 :221-37. Epub 1900 01 01.

Blocking S-adenosylmethionine synthesis in yeast allows selenomethionine incorporation and multiwavelength anomalous dispersion phasing.

Malkowski MG, Quartley E, Friedman AE, Babulski J, Kon Y, Wolfley J, Said M, Luft JR, Phizicky EM, DeTitta GT, Grayhack EJ

Proceedings of the National Academy of Sciences of the United States of America.. 2007 April 17104 (16):6678-83. Epub 04/10/2007.

The 2'-O-methyltransferase responsible for modification of yeast tRNA at position 4.

Wilkinson ML, Crary SM, Jackman JE, Grayhack EJ, Phizicky EM

RNA.. 2007 March 13 (3):404-13. Epub 01/22/2007.

Characteristics affecting expression and solubilization of yeast membrane proteins.

White MA, Clark KM, Grayhack EJ, Dumont ME

Journal of molecular biology.. 2007 January 19365 (3):621-36. Epub 10/06/2006.

Identification and characterization of modification enzymes by biochemical analysis of the proteome.

Jackman JE, Kotelawala L, Grayhack EJ, Phizicky EM

Methods in enzymology.. 2007 425 :139-52. Epub 1900 01 01.

Rapid tRNA decay can result from lack of nonessential modifications.

Alexandrov A, Chernyakov I, Gu W, Hiley SL, Hughes TR, Grayhack EJ, Phizicky EM

Molecular cell.. 2006 January 621 (1):87-96. Epub 1900 01 01.

Proteome-scale analysis of biochemical activity.

Phizicky EM, Grayhack EJ

Critical reviews in biochemistry and molecular biology. 2006 41 (5):315-27. Epub 1900 01 01.

Biochemical and genetic analysis of the yeast proteome with a movable ORF collection.

Gelperin DM, White MA, Wilkinson ML, Kon Y, Kung LA, Wise KJ, Lopez-Hoyo N, Jiang L, Piccirillo S, Yu H, Gerstein M, Dumont ME, Phizicky EM, Snyder M, Grayhack EJ

Genes & development.. 2005 December 119 (23):2816-26. Epub 1900 01 01.

Depletion of Saccharomyces cerevisiae tRNA(His) guanylyltransferase Thg1p leads to uncharged tRNAHis with additional m(5)C.

Gu W, Hurto RL, Hopper AK, Grayhack EJ, Phizicky EM

Molecular and cellular biology.. 2005 September 25 (18):8191-201. Epub 1900 01 01.

Pseudouridylation of yeast U2 snRNA is catalyzed by either an RNA-guided or RNA-independent mechanism.

Ma X, Yang C, Alexandrov A, Grayhack EJ, Behm-Ansmant I, Yu YT

The EMBO journal.. 2005 July 624 (13):2403-13. Epub 06/16/2005.

tRNA m7G methyltransferase Trm8p/Trm82p: evidence linking activity to a growth phenotype and implicating Trm82p in maintaining levels of active Trm8p.

Alexandrov A, Grayhack EJ, Phizicky EM

RNA.. 2005 May 11 (5):821-30. Epub 04/05/2005.

A facile method for high-throughput co-expression of protein pairs.

Alexandrov A, Vignali M, LaCount DJ, Quartley E, de Vries C, De Rosa D, Babulski J, Mitchell SF, Schoenfeld LW, Fields S, Hol WG, Dumont ME, Phizicky EM, Grayhack EJ

Molecular & cellular proteomics : MCP.. 2004 September 3 (9):934-8. Epub 07/07/2004.

The essential transcription factor Reb1p interacts with the CLB2 UAS outside of the G2/M control region.

Van Slyke C, Grayhack EJ

Nucleic acids research.. 2003 August 131 (15):4597-607. Epub 1900 01 01.

Biochemical genomics approach to map activities to genes.

Phizicky EM, Martzen MR, McCraith SM, Spinelli SL, Xing F, Shull NP, Van Slyke C, Montagne RK, Torres FM, Fields S, Grayhack EJ

Methods in enzymology.. 2002 350 :546-59. Epub 1900 01 01.

Genomic analysis of biochemical function.

Grayhack EJ, Phizicky EM

Current opinion in chemical biology.. 2001 February 5 (1):34-9. Epub 1900 01 01.

A biochemical genomics approach for identifying genes by the activity of their products.

Martzen MR, McCraith SM, Spinelli SL, Torres FM, Fields S, Grayhack EJ, Phizicky EM