Current Research
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.

Figure 1: The ENE confers stability...

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.

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