Charles Yanofsky (April 17, 1925[1] – March 16, 2018) was an Americangeneticist on the faculty of Stanford University who contributed to the establishment of the one gene-one enzyme hypothesis and discovered attenuation, a riboswitch mechanism in which messenger RNA changes shape in response to a small molecule and thus alters its binding ability for the regulatory region of a gene or operon.
Charles Yanofsky was born on April 17, 1925, inNew York.[2] He was one of the earliest graduates of the Bronx High School of Science,[3] then studied at theCity College of New York and completed his degree in biochemistry in spite of having had his education interrupted by military service in World War II including participation in the Battle of the Bulge.[2] In 1948, having returned and completed college, he took up graduate work towards his master's degree and PhD, both granted byYale University.[2] He pursued postdoctoral work at Yale for a time, completing work started during his PhD training.[3]
Yanofsky joined the Case Western Reserve Medical School faculty in 1954.[2][3] He moved to the faculty at Stanford University as an associate professor in 1958.[2] In 1964, Yanofsky and colleagues established thatgene sequences andprotein sequences are colinear in bacteria.[4] Yanofsky showed that changes inDNA sequence can produce changes in protein sequence at corresponding positions.[5] His work is considered the best evidence in favor of the one gene-one enzyme hypothesis.
His graduate studentIwona Stroynowski andMitzi Kuroda discovered the process of attenuation of expression based on regulated binding ability of thefive-prime untranslated region of themessenger RNA for the bacterial tryptophan operon. They had thus discovered the first regulatoryriboswitch,[6] although that terminology was not used until later. Yanofsky and his other collaborators then extended this work showing how mRNAs responded allosterically to a small molecule signal by changing shape and therefore changing ability to bind to the regulatory region of each operon. They showed that this mechanism applied to other amino acid biosynthesis and degradation operons of bacteria and to animal cell genes.[7]
In 1980, Yanofsky and other Stanford scientists founded DNAX, a Palo Alto–based research institute subsequently acquired by Schering-Plough.[3]
Yanofsky died inPalo Alto, California. At the time of death, he was the Morris Herzstein Professor of Biology and Molecular Biology (Emeritus) in the Department of Biology atStanford University.[2]
Yanofsky, Charles (2007), "RNA-based regulation of genes of tryptophan synthesis and degradation, in bacteria",RNA, vol. 13, no. 8 (published August 2007), pp. 1141–54,doi:10.1261/rna.620507,PMC1924887,PMID17601995
Yanofsky, Charles (2005), "The Favorable Features of Tryptophan Synthase for Proving Beadle and Tatum's One Gene–One Enzyme Hypothesis",Genetics, vol. 169, no. 2 (published February 2005), pp. 511–6,doi:10.1093/genetics/169.2.511,PMC1449131,PMID15731515
Yanofsky, Charles (2004), "The different roles of tryptophan transfer RNA in regulating trp operon expression in E. coli versus B. subtilis",Trends Genet., vol. 20, no. 8 (published August 2004), pp. 367–74,doi:10.1016/j.tig.2004.06.007,PMID15262409
Yanofsky, C (2000), "Transcription Attenuation: Once Viewed as a Novel Regulatory Strategy",J. Bacteriol., vol. 182, no. 1 (published January 2000), pp. 1–8,doi:10.1128/JB.182.1.1-8.2000,PMC94232,PMID10613855
Yanofsky, C; Konan, K V; Sarsero, J P (1996), "Some novel transcription attenuation mechanisms used by bacteria",Biochimie, vol. 78, no. 11–12, pp. 1017–24,doi:10.1016/S0300-9084(97)86725-9,PMID9150880
Yanofsky, C (1988), "Transcription attenuation",J. Biol. Chem., vol. 263, no. 2 (published January 15, 1988), pp. 609–12,PMID3275656
Yanofsky, C; Platt, T; Crawford, I P; Nichols, B P; Christie, GE; Horowitz, H; Vancleemput, M; Wu, AM (1981), "The complete nucleotide sequence of the tryptophan operon of Escherichia coli",Nucleic Acids Res., vol. 9, no. 24 (published December 21, 1981), pp. 6647–68,doi:10.1093/nar/9.24.6647,PMC327632,PMID7038627
Yanofsky, C (1971), "Tryptophan biosynthesis in Escherichia coli. Genetic determination of the proteins involved",JAMA, vol. 218, no. 7 (published November 15, 1971), pp. 1026–35,doi:10.1001/jama.218.7.1026,PMID4940311
Yanofsky, C (1967), "Gene structure and protein structure",Harvey Lect., vol. 61, pp. 145–68,PMID5338072