Joan A. Steitz

Last updated
Joan Steitz
Joan A. Steitz in her office with models (cropped).jpg
Born
Joan Elaine Argetsinger

(1941-01-26) January 26, 1941 (age 83)
Minneapolis, Minnesota, US
Alma mater
Known for
  • discovery of sites, sequences, and mechanism for mRNA binding to ribosomes
  • first discovery of RNAs not directly involved in protein assembly
  • discovery of snRNPs and their role in splicing eukaryotic mRNAs out of longer transcripts
Spouse Thomas Steitz
Children1
Awards
Scientific career
Fields
Institutions
Thesis Studies of the R17A protein  (1968)
Doctoral advisor James D. Watson [4]
Doctoral students Sandra Wolin, Gia Voeltz
Website

Joan Elaine Argetsinger Steitz (born January 26, 1941) is Sterling Professor of Molecular Biophysics and Biochemistry at Yale University and Investigator at the Howard Hughes Medical Institute. She is known for her discoveries involving RNA, including ground-breaking insights into how ribosomes interact with messenger RNA by complementary base pairing and that introns are spliced by small nuclear ribonucleic proteins (snRNPs), which occur in eukaryotes. [5] [6] [7] [8] [9] In September 2018, Steitz won the Lasker-Koshland Award for Special Achievement in Medical Science. The Lasker award is often referred to as the 'American Nobel' because 87 of the former recipients have gone on to win Nobel prizes. [10]

Contents

Early life and education

Steitz was born in Minneapolis, Minnesota. [11] She grew up in Minnesota in the 1950s and 60s and attended the then all-girls Northrop Collegiate School for high school.

In 1963, Steitz received her Bachelor of Science degree in chemistry from Antioch College, Ohio, where she first became interested in molecular biology at Alex Rich's Massachusetts Institute of Technology laboratory as an Antioch "coop" intern.

After completing her undergraduate degree, Steitz applied to medical school rather than graduate school since she knew of female medical doctors but not women scientists. [12] She was accepted to Harvard Medical School, but having been excited by a summer working as a bench scientist in the laboratory of Joseph Gall at the University of Minnesota, she declined the invitation to Harvard Medical School and instead applied to Harvard's new program in biochemistry and molecular biology. There, she was the first female graduate student to join the laboratory of Nobel Laureate James Watson, with whom she first worked on bacteriophage RNA. [13]

Career

Steitz describes her excitement about research in the field of biology, her contributions, and their vast implications on health today.

Steitz completed postdoctoral research at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) at the University of Cambridge (UK), where she collaborated with Francis Crick, Sydney Brenner, and Mark Bretscher. At the LMB, Steitz focused on the question of how bacteria know where to start the "reading frame" on mRNA. In the process, Steitz discovered the exact sequences on a mature RNA virus encoding three proteins where the virus mRNA binds bacterial ribosomes to produce proteins. In 1969 she published a seminal paper in Nature showing the nucleotide sequence of the binding start points. [14]

In 1970, Steitz joined the faculty at Yale. In 1975, she published a research finding for which she is widely known, demonstrating that ribosomes use complementary base pairing to identify the start site on mRNA. [15] [16]

In 1980, Steitz in collaboration with Michael Lerner published another critical paper, using immunoprecipitation with human antibodies from patients with autoimmunity to isolate and identify snRNPs (pronounced "snurps") and detect their role in splicing. [5] A snRNP is a specific short length of RNA, around 150 nucleotides long, associated with protein, that is involved in splicing introns out of newly transcribed RNA (pre-mRNA), a component of the spliceosomes. Steitz's paper "set the field ahead by light years and heralded the avalanche of small RNAs that have since been discovered to play a role in multiple steps in RNA biosynthesis," noted Susan Berget. [12]

Steitz later discovered another kind of snRNP particle, the snoRNP, involved in an important minority of mRNA splicing reactions. Via analysis of the genetic locations of the genes for snoRNPs, she demonstrated conclusively that introns are not "junk DNA" as they had often been described. Her work helps explain the phenomenon of "alternative RNA splicing." [17] [18] Her discovery of the snRNPs and snoRNPs explains a mysterious finding: humans have only double the number of genes of a fruit fly. "The reason we can get away with so few genes is that when you have these bits of nonsense, you can splice them out in different ways," she said. "Sometimes you can get rid of things and add things because of this splicing process so that each gene has slightly different protein products that can do slightly different things. So it multiplies up the information content in each of our genes." [19]

Steitz's research [20] may yield new insights into the diagnosis and treatment of autoimmune disorders such as lupus, which develop when patients make anti-nuclear antibodies against their own DNA, snRNPs, or ribosomes. [21]

Steitz has commented on the sexist treatment of women in science, and has been a "tireless promoter of women in science," noted Christine Guthrie, who described Steitz as "one of the greatest scientists of our generation." [12]

Steitz has served in numerous professional capacities, including as scientific director of the Jane Coffin Childs Memorial Fund for Medical Research (1991–2002) and as editorial board member of Genes & Development .

Personal life

Steitz (born Joan Argetsinger) married Thomas Steitz, also Sterling Professor of Molecular Biophysics and Biochemistry at Yale and the 2009 Nobel Prize in Chemistry laureate, in 1966. They have one son, Jon. [22]

Awards and honors

Her nomination for the Royal Society reads:

Joan Steitz is one of the pioneers of the field of RNA biology who is world-renowned for her many seminal contributions. She showed how ribosomal RNA is used to initiate translation at the start site of mRNA. She discovered spliceosomes, the particles that are the sites of splicing of pre-messenger RNA into the final mature mRNA and elucidated many of their roles. She discovered that introns, which were thought to be inert, code for sno RNAs that target the modification of other cellular RNAs during their maturation. More recently she has found new roles for microRNAs in gene regulation. [3]

Related Research Articles

<span class="mw-page-title-main">RNA</span> Family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

<span class="mw-page-title-main">RNA splicing</span> Process in molecular biology

RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns and splicing back together exons. For nuclear-encoded genes, splicing occurs in the nucleus either during or immediately after transcription. For those eukaryotic genes that contain introns, splicing is usually needed to create an mRNA molecule that can be translated into protein. For many eukaryotic introns, splicing occurs in a series of reactions which are catalyzed by the spliceosome, a complex of small nuclear ribonucleoproteins (snRNPs). There exist self-splicing introns, that is, ribozymes that can catalyze their own excision from their parent RNA molecule. The process of transcription, splicing and translation is called gene expression, the central dogma of molecular biology.

<span class="mw-page-title-main">Spliceosome</span> Molecular machine that removes intron RNA from the primary transcript

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 specific proteins to form a small nuclear ribonucleoprotein complex, which in turn combines with other snRNPs to form a large ribonucleoprotein complex called a spliceosome. The spliceosome removes introns from a transcribed pre-mRNA, a type of primary transcript. This process is generally referred to as splicing. An analogy is a film editor, who selectively cuts out irrelevant or incorrect material from the initial film and sends the cleaned-up version to the director for the final cut.

snRNPs, or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs. The action of snRNPs is essential to the removal of introns from pre-mRNA, a critical aspect of post-transcriptional modification of RNA, occurring only in the nucleus of eukaryotic cells. Additionally, U7 snRNP is not involved in splicing at all, as U7 snRNP is responsible for processing the 3′ stem-loop of histone pre-mRNA.

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 transcribed by either RNA polymerase II or RNA polymerase III. Their primary function is in the processing of pre-messenger RNA (hnRNA) in the nucleus. They have also been shown to aid in the regulation of transcription factors or RNA polymerase II, and maintaining the telomeres.

<span class="mw-page-title-main">Minor spliceosome</span>

The minor spliceosome is a ribonucleoprotein complex that catalyses the removal (splicing) of an atypical class of spliceosomal introns (U12-type) from messenger RNAs in some clades of eukaryotes. This process is called noncanonical splicing, as opposed to U2-dependent canonical splicing. U12-type introns represent less than 1% of all introns in human cells. However they are found in genes performing essential cellular functions.

<span class="mw-page-title-main">Small nucleolar RNA SNORD115</span>

In molecular biology, SNORD115 is a non-coding RNA (ncRNA) molecule known as a small nucleolar RNA which usually functions in guiding the modification of other non-coding RNAs. This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. HBII-52 refers to the human gene, whereas RBII-52 is used for the rat gene and MBII-52 is used for naming the mouse gene.

<span class="mw-page-title-main">Small nucleolar RNA SNORD29</span>

In molecular biology, SNORD29 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD36</span>

In molecular biology, snoRNA U36 is a non-coding RNA (ncRNA) molecule which functions in the biogenesis (modification) of other small nuclear RNAs (snRNAs). This type of modifying RNA is located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD62</span>

In molecular biology, snoRNA U62 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">Small nucleolar RNA SNORD83</span>

In molecular biology, Small nucleolar RNA SNORD83 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA. snoRNA SNORD83 belongs to the C/D box class of snoRNAs which contain the conserved sequence motifs known as the C box (UGAUGA) and the D box (CUGA). Most of the members of the box C/D family function in directing site-specific 2'-O-methylation of substrate RNAs. snoRNA SNORD83 are spliced from introns 5 and 4 of the BAT1 gene in mammals.

<span class="mw-page-title-main">Small nucleolar RNA TBR7</span>

In molecular biology, Small nucleolar RNA TBR7 is a non-coding RNA (ncRNA) molecule identified in Trypanosoma brucei which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.

<span class="mw-page-title-main">U2 spliceosomal RNA</span>

U2 spliceosomal snRNAs are a species of small nuclear RNA (snRNA) molecules found in the major spliceosomal (Sm) machinery of virtually all eukaryotic organisms. In vivo, U2 snRNA along with its associated polypeptides assemble to produce the U2 small nuclear ribonucleoprotein (snRNP), an essential component of the major spliceosomal complex. The major spliceosomal-splicing pathway is occasionally referred to as U2 dependent, based on a class of Sm intron—found in mRNA primary transcripts—that are recognized exclusively by the U2 snRNP during early stages of spliceosomal assembly. In addition to U2 dependent intron recognition, U2 snRNA has been theorized to serve a catalytic role in the chemistry of pre-RNA splicing as well. Similar to ribosomal RNAs (rRNAs), Sm snRNAs must mediate both RNA:RNA and RNA:protein contacts and hence have evolved specialized, highly conserved, primary and secondary structural elements to facilitate these types of interactions.

<span class="mw-page-title-main">U6 spliceosomal RNA</span> Small nuclear RNA component of the spliceosome

U6 snRNA is the non-coding small nuclear RNA (snRNA) component of U6 snRNP, an RNA-protein complex that combines with other snRNPs, unmodified pre-mRNA, and various other proteins to assemble a spliceosome, a large RNA-protein molecular complex that catalyzes the excision of introns from pre-mRNA. Splicing, or the removal of introns, is a major aspect of post-transcriptional modification and takes place only in the nucleus of eukaryotes.

<span class="mw-page-title-main">PRPF8</span> Protein-coding gene in the species Homo sapiens

Pre-mRNA-processing-splicing factor 8 is a protein that in humans is encoded by the PRPF8 gene.

<span class="mw-page-title-main">Thomas A. Steitz</span> American biochemist (1940–2018)

Thomas Arthur Steitz was an American biochemist, a Sterling Professor of Molecular Biophysics and Biochemistry at Yale University, and investigator at the Howard Hughes Medical Institute, best known for his pioneering work on the ribosome.

Messenger RNP is mRNA with bound proteins. mRNA does not exist "naked" in vivo but is always bound by various proteins while being synthesized, spliced, exported, and translated in the cytoplasm.

<span class="mw-page-title-main">Sandra Wolin</span> American microbiologist and physician-scientist

Sandra Lynn Wolin is an American microbiologist and physician-scientist specialized in biogenesis, function, and turnover of non-coding RNA. She is chief of the RNA Biology Laboratory at the National Cancer Institute.

Christine Guthrie (1945-2022) was an American yeast geneticist and American Cancer Society Research Professor of Genetics at University of California San Francisco. She showed that yeast have small nuclear RNAs (snRNAs) involved in splicing pre-messenger RNA into messenger RNA in eukaryotic cells. Guthrie cloned and sequenced 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. She also identified proteins that formed part of the spliceosome complex with the snRNAs. Elected to the National Academy of Sciences in 1993, Guthrie edited Guide to Yeast Genetics and Molecular Biology, an influential methods series for many years.

<span class="mw-page-title-main">Susan J. Baserga</span> American physician and academic

Susan J. Baserga is an American physician who is the William H. Fleming Professor of Molecular Biophysics and Biochemistry at Yale University. Her research considers the molecular basis of ribosomes, and the mechanistic basis of inherited human disease.

References

  1. ↑ Joan A. Steitz, Yale University, nasonline.org
  2. 1 2 "Joan A. Steitz (1941– )". National Medal of Science 50th Anniversary. National Science Foundation. Retrieved 8 May 2014.
  3. 1 2 "Professor Joan Steitz ForMemRS". London: The Royal Society. Archived from the original on 2014-12-20.
  4. ↑ Steitz, J (2011). "Joan Steitz: RNA is a many-splendored thing. Interview by Caitlin Sedwick". The Journal of Cell Biology. 192 (5): 708–09. doi:10.1083/jcb.1925pi. PMC   3051824 . PMID   21383073.
  5. 1 2 Lerner, M. R.; Boyle, J. A.; Mount, S. M.; Wolin, S. L.; Steitz, J. A. (1980). "Are snRNPs involved in splicing?". Nature. 283 (5743): 220–24. Bibcode:1980Natur.283..220L. doi:10.1038/283220a0. PMID   7350545. S2CID   4266714.
  6. ↑ Vasudevan, S.; Tong, Y.; Steitz, J. A. (2007). "Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation". Science. 318 (5858): 1931–34. Bibcode:2007Sci...318.1931V. doi:10.1126/science.1149460. PMID   18048652. S2CID   6173875.
  7. ↑ Steitz, T. A.; Steitz, J. A. (1993). "A general two-metal-ion mechanism for catalytic RNA". Proceedings of the National Academy of Sciences of the United States of America. 90 (14): 6498–502. Bibcode:1993PNAS...90.6498S. doi: 10.1073/pnas.90.14.6498 . PMC   46959 . PMID   8341661.
  8. ↑ Joan Steitz (Yale & HHMI): SNURPs and Serendipity on YouTube, iBioMagazine
  9. ↑ Friedberg, E. C. (2008). "Joan Steitz interview". Nature Reviews Molecular Cell Biology. 9 (6): 428. doi:10.1038/nrm2421. S2CID   46399783.
  10. 1 2 Thomas, Katie (11 September 2018). "Lasker Awards Given for Work in Genetics, Anesthesia and Promoting Women in Science". The New York Times. Retrieved 2018-09-11.
  11. ↑ Steitz CV, Yale
  12. 1 2 3 ASCB Profile: Joan Argetsinger Steitz, June 2006.
  13. ↑ Margaret A. Woodbury, "Trailblazer Turned Superstar," Archived 2008-10-06 at the Wayback Machine HHMI Bulletin, Feb. 2006.
  14. ↑ Steitz, J. A. (1969). "Polypeptide Chain Initiation: Nucleotide Sequences of the Three Ribosomal Binding Sites in Bacteriophage R17 RNA". Nature. 224 (5223): 957–64. Bibcode:1969Natur.224..957S. doi:10.1038/224957a0. PMID   5360547. S2CID   4179670.
  15. ↑ Steitz, J. A.; Jakes, K (1975). "How ribosomes select initiator regions in mRNA: Base pair formation between the 3' terminus of 16S rRNA and the mRNA during initiation of protein synthesis in Escherichia coli". Proceedings of the National Academy of Sciences of the United States of America. 72 (12): 4734–38. Bibcode:1975PNAS...72.4734S. doi: 10.1073/pnas.72.12.4734 . PMC   388805 . PMID   1107998.
  16. ↑ Joan Steitz – Biography, Cold Spring Harbor Laboratory Digital archives
  17. ↑ Thomas R. Cech and Joan A Steitz (2014) “The Noncoding RNA Revolution Trashing the Old Rules to Forge New Ones.” Cell157 (1): 77–94.
  18. ↑ Woan-Yuh Tam and Joan A. Steitz, (1997) “Pre-mRNA splicing: the discovery of a new spliceosome doubles the challenge. – Trends in Biochemical Sciences22(4): 132–37.
  19. ↑ Elaine Carey, "Female scientist 'a hero in her field': Yale's Joan Steitz, 65 honoured", Toronto Star April 3, 2006, p. A04; ( "The Gairdner Foundation". Archived from the original on September 27, 2007. Retrieved 2006-11-27.).
  20. ↑ Joan Steitz publications in Google Scholar
  21. ↑ Lerner, M. R.; Steitz, J. A. (1979). "Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus". Proceedings of the National Academy of Sciences of the United States of America. 76 (11): 5495–99. doi: 10.1073/pnas.76.11.5495 . PMC   411675 . PMID   316537.
  22. ↑ Gonzalez, Susan (June 29, 2011). "Yale pitcher is grabbed in draft's early rounds". Yale Bulletin & Calendar. Archived from the original on April 2, 2015. Retrieved February 3, 2014.
  23. ↑ Wolf Prize in Medicine 2021
  24. ↑ "Prize lecture winners 2021". The Microbiology Society. Retrieved 26 November 2020.
  25. ↑ "Joan A. Steitz". Royal Society of London. Retrieved September 20, 2018.
  26. ↑ "Jubilee Lecture". The Biochemical Society. Retrieved September 13, 2018.
  27. ↑ Honorary Degree Recipients for 2011 Announced Archived 2011-05-21 at the Wayback Machine , Columbia University
  28. ↑ "Albany Medical Center Award". Albany Medical Center. May 2, 2008. Retrieved September 13, 2018.
  29. ↑ "Rosalind E. Franklin Award". National Cancer Institute Center for Cancer Research. Retrieved September 13, 2018.
  30. ↑ "Joan A. Steitz". Gairdner Foundation. Retrieved September 13, 2018.
  31. ↑ "E. B. Wilson Medal". American Society for Cell Biology. Retrieved September 13, 2018.
  32. ↑ "August Newsletter of the RNA Society" (PDF). The RNA Society. Retrieved September 13, 2018.
  33. ↑ "Caledonian Research Fund Prize Lectureship". The Royal Society of Edinburgh. Retrieved September 13, 2018.
  34. ↑ "FASEB Excellence in Science Award" (PDF). Federation of American Societies of Experimental Biology. Retrieved September 20, 2018.
  35. ↑ "Lewis S. Rosenstiel Award". Brandeis University. Retrieved September 20, 2018.
  36. ↑ "L'Oreal-UNESCO Awards for Women in Science". L'Oreal. Retrieved September 20, 2018.
  37. ↑ "Golden Plate Awardees of the American Academy of Achievement". www.achievement.org. American Academy of Achievement.
  38. ↑ "APS Member History". search.amphilsoc.org. Retrieved 2022-04-01.
  39. ↑ "Warren Triennial Prize". Harvard University. Retrieved September 20, 2018.
  40. ↑ "Dickson Prize Past Winners". Carnegie Mellon University. Retrieved September 20, 2018.
  41. ↑ "National Medal of Science Recipient Details". National Science Foundation. Retrieved September 20, 2018.
  42. 1 2 "Joan A. Steitz". National Academy of Sciences members. Retrieved September 13, 2018.
  43. ↑ "Past Howley Prize Recipients". Arthritis.org. Retrieved September 20, 2018.
  44. ↑ "Joan A. Steitz". American Academy of Arts and Sciences. Retrieved September 20, 2018.
  45. ↑ "Lilly Awardees" (PDF). ACS Biological Chemistry Division. Archived from the original (PDF) on October 9, 2020. Retrieved September 20, 2018.
  46. ↑ "Services (Young Scientist Award)". Passano Foundation. Retrieved September 20, 2018.

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