Christine Guthrie (1945-2022) was an American yeast

geneticist A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic processe ...

and American Cancer Society Research Professor of Genetics at

University of California San Francisco The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It condu ...

. She showed that yeast have

small nuclear RNA Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the splicing speckles and Cajal bodies of the cell nucleus in eukaryotic cells. The length of an average snRNA is approximately 150 nucleotides. They are transcribe ...

s (snRNAs) involved in splicing pre-messenger RNA into

messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the p ...

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

cells. Guthrie

cloned Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, c ...

and

sequenced In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which suc ...

the genes for yeast snRNA and established the role of base pairing between the snRNAs and their target sequences at each step in the removal of an

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...

. She also identified proteins that formed part of the

spliceosome A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specifi ...

complex with the snRNAs. Elected to the

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...

in 1993, Guthrie edited ''Guide to Yeast Genetics and Molecular Biology'', an influential methods series for many years.

Early life and education

Christine Guthrie was born in Brooklyn, New York. She received a BS in Zoology from

University of Michigan , mottoeng = "Arts, Knowledge, Truth" , former_names = Catholepistemiad, or University of Michigania (1817–1821) , budget = $10.3 billion (2021) , endowment = $17 billion (2021)As o ...

and a PhD in genetics from University of Wisconsin. Her PhD advisor was

Masayasu Nomura was a Japanese molecular biologist. Nomura was born in April 1927, a native of Hyōgo Prefecture, and completed a bachelor's degree and doctorate at the University of Tokyo. Nomura began work in 1957 as a postdoctoral researcher in the United S ...

. She was the daughter of Brooklyn native and humorist Irene Kampen, whose book, Life Without George, was the basis for The Lucy Show, which aired for six seasons on CBS in the 1960s. (Lucy's daughter on the show was named Chris.)

Academic career

In 1973, she was hired as an assistant professor at University of California, San Francisco (UCSF). After a tough pre-tenure review in 1976, she found support in a group of women and men who met informally for 20 years to help each other thrive in academia. She was a professor of biochemistry and American Cancer Society Research Professor of Genetics at UCSF. Saccharomyces cerevisiae SEM

Research

Guthrie showed that yeast have introns in their pre-messenger RNAs. They also have small nuclear RNAs (snRNAs) involved in splicing pre-messenger RNA into messenger RNA in eukaryotic cells. 2 In work described in her citation for the Genetics Society of America Medal as a “macromolecular tour de force”, she cloned and sequenced the ''SNR'' genes for the yeast snRNAs. To accomplish this feat, she had to invent methods to discriminate functional snRNAs from degradation products and also to create widely used intron-containing

reporter gene In molecular biology, a reporter gene (often simply reporter) is a gene that researchers attach to a regulatory sequence of another gene of interest in bacteria, cell culture, animals or plants. Such genes are called reporters because the charac ...

s. Her work established the role of base pairing between the snRNAs and their target sequences at each step in the removal of an intron and allowed identification of proteins that formed part of the spliceosome complex with the snRNAs.

Personal life

Guthrie was married to

John Abelson John Norman Abelson (born 1938 in Grand Coulee, WashingtonNicole Kresge, Robert D. Simoni and Robert L. Hill, 2009DNA Transcription and tRNA Ligase: the Work of John Abelson The Journal of Biological Chemistry, 284, e20-21.) is an American molec ...

biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...

and geneticist.

Awards

* 1993

* 1997

Genetics Society of America Medal The Genetics Society of American Medal is a medal awarded by the Genetics Society of America (GSA) for outstanding contributions to the field of genetics in the last 15 years. The Medal was established by society in 1981 and recognizes members who ...

* 1998 WICB Senior Career Recognition Award (

American Society for Cell Biology The American Society for Cell Biology (ASCB) is a professional society that was founded in 1960. * 2011 ASBMB-Merck Award

Works

Selected scientific papers

* Brow D. A., Guthrie C., 1988 “Spliceosomal RNA U6 is remarkably conserved from yeast to mammals.” ''Nature'' 334'':'' 213–218. * Burgess S., Couto J. R., Guthrie C., 1990 “A putative ATP binding protein influences the fidelity of branchpoint recognition in yeast splicing.” ''Cell'' 60: 705–717. * Burgess S. M., Guthrie C.'', 1993 “''A mechanism to enhance mRNA splicing fidelity: the RNA-dependent ATPase Prp16 governs usage of a discard pathway for aberrant lariat intermediates.''” Cell'' 73'':'' 1377–1391''.'' * Cellini A., Parker R., McMahon J., Guthrie C., Rossi J.'','' 1986 “Activation of a cryptic TACTAAC box in the Saccharomyces cerevisiae actin intron.” ''Mol. Cell Biol.'' 6: 1571–1578. * Couto J. R., Tamm J., Parker R., Guthrie C.'','' 1987 “A trans-acting suppressor restores splicing of a yeast intron with a branch point mutation.” ''Genes Dev.'' 1: 445–455. * Guthrie C.'','' 1991 ''“''Messenger RNA splicing in yeast: clues to why the spliceosome is a ribonucleoprotein.” ''Science'' 253: 157–163. * Guthrie C., Nashimoto H., Nomura M., 1969 “Structure and function of E. coli ribosomes. 8. Cold-sensitive mutants defective in ribosome assembly.” ''Proc. Natl. Acad. Sci. USA'' 63: 384–391. * Guthrie C., Patterson B., 1988 “Spliceosomal snRNAs.” ''Annu. Rev. Genet.'' 22: 387–419. * Jandrositz A., Guthrie C., 1995 “Evidence for a Prp24 binding site in U6 snRNA and in a putative intermediate in the annealing of U6 and U4 snRNAs.” ''Euro Mol Biol Org J.'' 14: 820–832. * Lesser C. F., Guthrie C. 1993 “Mutations in U6 snRNA that alter splice site specificity: Implications for the active site.” ''Science'' 262: 1982–1988. * Madhani H. D., Bordonne R., Guthrie C. 1990 “Multiple roles for U6 snRNA in the splicing pathway.” ''Genes Dev''. 4: 2264–2277. * Madhani H. D., Guthrie C., 1992 “A novel base-pairing interaction between U2 and U6 snRNAs suggests a mechanism for the catalytic activation of the spliceosome.” ''Cell'' 71: 803–817. * Madhani H. D., Guthrie C., 1994 “Dynamic RNA-RNA interactions in the spliceosome.” ''Annu. Rev. Genet.'' 28: 1–26. * Noble S. M., Guthrie C., 1996 “Identification of novel genes required for yeast pre-mRNA splicing by means of cold-sensitive mutations.” ''Genetics'' 143: 67–80. * Parker R., Guthrie C., 1985 “A point mutation in the conserved hexanucleotide at a yeast 5′ splice junction uncouples recognition, cleavage, and ligation.” ''Cell'' 41: 107–118. * Parker R., Siliciano P. G., Guthrie C., 1987 “Recognition of the TACTAAC box during mRNA splicing in yeast involves base pairing to the U2-like snRNA.” ''Cell'' 49: 229–239. * Patterson B., Guthrie C., 1987 “An essential yeast snRNA with a U5-like domain is required for splicing in vivo.” ''Cell'' 49: 613–624. * Riedel N., Wise J. A., Swerdlow H., Mak A., Guthrie C., 1986 “Small nuclear RNAs from Saccharomyces cerevisiae: unexpected diversity in abundance, size, and molecular complexity.” ''Proc Natl. Acad. Sci. USA'' 83: 8097–8101. * Schwer B., Guthrie C., 1991 “PRP16 is an RNA-dependent ATPase that interacts transiently with the spliceosome.” ''Nature'' 349: 494–499. * Schwer B., Guthrie C., 1992 “A conformational rearrangement in the spliceosome is dependent on PRP16 and ATP hydrolysis.” E''uro Mol Bio Org J.'' 11: 5033–5039. * Shannon K. W., Guthrie C., 1991 “Suppressors of a U4 snRNA mutation define a novel U6 snRNP protein with RNA-binding motifs.” ''Genes Dev.'' 5: 773–785. * Siliciano P. G., Brow D. A., Roiha H., Guthrie C., 1987a “An essential snRNA from S. cerevisiae has properties predicted for U4, including interaction with a U6-like snRNA.” ''Cell'' 50: 585–592. * Siliciano P. G., Jones M. H., Guthrie C., 1987b “Saccharomyces cerevisiae has a U1-like small nuclear RNA with unexpected properties.” ''Science'' 237: 1484–1487. * Siliciano P. G., Guthrie C., 1988 “5′ splice site selection in yeast: genetic alterations in base-pairing with U1 reveal additional requirements.” ''Genes Dev''. 2: 1258–1267. * Strauss E. J., Guthrie C., 1991 “A cold-sensitive mRNA splicing mutant is a member of the RNA helicase gene family.” ''Genes Dev.'' 5: 629–641. * Vijayraghavan U., Parker R., Tamm J., Iimura Y., Rossi J., et al., 1986 “Mutations in conserved intron sequences affect multiple steps in the yeast splicing pathway, particularly assembly of the spliceosome.” E''uro Mol Bio Org J''. 5: 1683–1695. * Wise J. A., Tollervey D., Maloney D., Swerdlow H., Dunn E. J., et al., 1983 “Yeast contains small nuclear RNAs encoded by single copy genes.” ''Cell'' 35: 743–751.

Books

* Christine Guthrie, editor 2002 ''Guide to Yeast Genetics and Molecular and Cell Biology'', Part B, ''Methods in Enzymology'' Volume 350 Academic Press. * Christine Guthrie and Gerald R. Fink, editors. 2002 ''Guide to Yeast Genetics and Molecular and Cell Biology'', Part A ''Methods in Enzymology'' volume 351 Academic Press. * Christine Guthrie and Gerald R. Fink, editors. 2002 ''Guide to Yeast Genetics and Molecular Cell Biology'' Part B ''Methods in Enzymology'' volume 351 Academic Press. * Christine Guthrie and Gerald R. Fink, editors. 2002 ''Guide to Yeast Genetics and Molecular Cell Biology'' Part C ''Methods in Enzymology'' volume 351 Academic Press. * Jonathan Weisman, Christine Guthrie, and Gerald Fink editors, 2010. Guide to Yeast Genetics: Functional Genomics, Proteomics and other Systems Analysis. ''Methods in Enzymology'' volume 470 2nd edition Academic Press.

References

{{DEFAULTSORT:Guthrie, Christine American women geneticists Living people American geneticists Scientists from Brooklyn University of California, San Francisco faculty University of Michigan alumni University of Wisconsin–Madison College of Agricultural and Life Sciences alumni Members of the United States National Academy of Sciences Scientists from New York (state) Fellows of the American Academy of Microbiology 1945 births