Biochemistry, Molecular Biology
Dr. Steitz is also Sterling Professor of Molecular Biophysics and Biochemistry at Yale School of Medicine.
RNA Machines of the Mammalian Cell Nucleus
Joan Steitz is a pioneer in the study of small, noncoding RNA molecules, which are essential for gene expression in most cells.
One focus of Steitz’s research is small nuclear ribonucleoproteins, or snRNPs, which are tightly bound complexes of proteins and small noncoding RNAs. Steitz’s lab group discovered snRNPs in 1979 and showed that they are critical for the removal of introns – segments of genetic material that interrupt a gene’s protein-coding sequence.
Introns are copied into an RNA molecule along with the rest of a gene, and must be removed before the RNA can be used as a template for protein synthesis. The removal process, called splicing, takes place in large snRNP-protein complexes called spliceosomes that assemble directly on introns. After showing that snRNPs are essential for splicing, Steitz’s lab deciphered how particular snRNPs recognize intron splice sites.
Steitz’s subsequent work has identified additional snRNPs that participate in the excision of different types of introns (mRNAs) and in developmentally controlled mRNA processing. Her group has also discovered small nucleolar RNAs (snoRNAs), which ready a different type of RNA – ribosomal RNA – as a building material for cells’ protein factories, trimming precursor molecules to the right size and chemically modifying them in precise ways.
Even smaller bits of noncoding RNA, called microRNAs, influence the stability of mRNA molecules and their translation into proteins. Steitz’s work has helped explain how microRNAs are generated and processed inside cells.
Steitz also investigates how viruses use noncoding RNAs to manipulate host cells. Her group has found that a herpes virus causes T cell lymphoma in monkeys by using a snRNP to degrade host microRNA, releasing the brake on growth-promoting genes. Her group’s work has also uncovered the function of noncoding RNAs generated by two other cancer-causing viruses, the Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus.
As a college student in the 1960s, Joan Steitz never imagined herself as a topflight scientist. Certainly, she was fascinated by science. She even assisted senior scientists in laboratories at the Massachusetts Institute of Technology, where she befriended James D. Watson, codiscoverer of the DNA double helix, and at the Max Planck Institute in Germany. But when it came time to choose a career path, Steitz had convinced herself that she was not devoted enough to spend grueling nights and weekends in the lab.
What’s more, she was discouraged by the lack of female role models. “When I was a graduate student, there were no women professors in the biological sciences at any major university,” Steitz recalls. “Consequently, I never envisioned myself being where I am today.”
She applied to medical school and was accepted at Harvard. After graduating from college, though, Steitz took a summer job in a research lab at the University of Minnesota, under the supervision of cell biologist Joseph Gall. He set Steitz up with her own project: determining whether ciliary basal bodies from the protozoan Tetrahymena pyriformis contain nucleic acid.
Suddenly, Steitz found herself working nights and weekends, and enjoying it. By August, and with Gall’s encouragement, she decided to change her career plans.
In 1963, Steitz became the sole woman in a class of 10 to begin graduate studies in biochemistry and molecular biology at Harvard, and the first female graduate student to work under Watson’s guidance. “He was an excellent mentor and very supportive of my work,” says Steitz, whose early research focused on RNA structure and function in bacteria. “He was truly an inspiration and taught me to focus on the important questions in science.”
Today, Steitz is best known for discovering and defining the function of small nuclear ribonucleoproteins (snRNPs), which occur only in higher cells and organisms. These cellular complexes play a key role in the splicing of pre-messenger RNA (pre-mRNA), the earliest product of DNA transcription. Both DNA and pre-mRNA typically contain numerous nonsense segments called introns. Working in the nucleus, snRNPs excise the introns from pre-mRNA and splice together the resulting segments, which together make up messenger RNA (mRNA). The mRNAs contain the “recipes” for making proteins, which are critical for carrying out the body’s most basic biological processes.
Steitz’s research may yield new insights into the diagnosis and treatment of lupus, an autoimmune disease that develops when patients make antibodies against their own DNA, snRNPs, or ribosomes – the body’s protein-making factories. She and her colleagues are also studying other snRNPs involved in excising a rare, divergent class of introns, and still other snRNPs involved in pre-ribosomal RNA processing.
Steitz is married to HHMI Investigator and Nobel Laureate Thomas Steitz, also at Yale University. The two researchers have coauthored two papers, in 1993 and in 2010. Having a spouse who understands “the pressures and joys of a career in academic science makes it all possible,” says Steitz.