Joan A. Steitz

Joan Steitz held out against a research career until she could resist no longer. Undergraduate stints as a lab technician in the early 1960s introduced her to the new and effervescent world of molecular genetics. The subject fascinated her, but she knew of no female biology professors. She decided to become a physician.

The summer before medical school, Steitz took another lab job—this time as an independent researcher. She relished the responsibility and the thrill of discovery. Even if she couldn’t run a lab, she could conduct her own experiments in someone else’s. In the fall, she entered a Ph.D. program.

By her postdoc, Steitz still did not foresee a future professorship, so she embarked on a risky and challenging project—one that numerous male colleagues had rejected. Unlike them, she did not need results that would ensure a strong academic job application.
Scientists knew that molecular machines called ribosomes translate genetic information from messenger RNAs (mRNAs) into protein—and that bacterial ribosomes somehow find their starting points in the middle of mRNA molecules. As a step toward understanding that homing process, researchers wanted to isolate and sequence the target stretch of mRNA. Relevant techniques were in their infancy, however, and no one had dared attempt the task. After a year, Steitz prevailed.

That 1969 triumph propelled her onto the international stage as the women’s movement began prying open university doors. Six years later, as a faculty member, she tackled the next issue: How do ribosomes pinpoint their start sites? She discovered that the same force that holds together the DNA helix—base pairing—recruits an RNA component of the ribosome to the correct spot on mRNAs. This revelation forced scientists to rethink ribosomal RNAs: They were not just scaffolds for ribosomal proteins, but key players in protein synthesis.

In the meantime, perplexing information was emerging. Ninety percent of mammalian RNA disappears as soon as it’s made. No one knew why cells expend energy producing RNA only to destroy it.

In 1977, researchers uncovered an unanticipated process that explained that conundrum. After mammals make an RNA copy of their DNA, they remove internal sequences, dubbed introns, to craft mature mRNAs that serve as protein templates.
Molecular machinery must splice the precursor RNA, and Steitz wanted to track it down. She recognized and developed a powerful tool for pursuing this endeavor: autoimmune antibodies that bind ill-defined nuclear conglomerations of RNA and protein. Given the location and abundance of these RNA/protein complexes, she speculated that they contribute to splicing. Using the antibodies, Steitz and her student Michael Lerner identified distinct entities, each of which contained a specific small nuclear RNA (snRNA) and common proteins. She named the particles small nuclear ribonucleoproteins (snRNPs).

She noticed that one snRNA contains a sequence that aligns with the splice sites of precursor mRNAs. This observation and others led to confirmation of her idea and fueled a burst of knowledge about the intricate system by which snRNPs and other molecules remove introns.

Steitz has unveiled secrets not only about splicing, but also about the ever-growing family of small RNAs that do not encode proteins. These unforeseen yet mighty molecules perform numerous essential physiological processes.

Author: Evelyn Strauss, Ph.D.