Dr. Louise Chow
“Of course it is obvious it is splicing – it’s cut and paste – just like film editing”
Dr. Chow on discovering RNA splicing, on Virology Unmasked, 2026
Episode also available through Spotify, Apple, and Podbean
Throughout Dr. Chow’s 50+ year career, she made many invaluable contributions to science. Her work started in the field of electron microscopy (EM). She started at Cal Tech studying the transcription of bacteria and the phage which infect them. She then moved to the Cold Spring Harbor Laboratory (CSHL) where she started a joint lab with her husband, Dr. Thomas Broker. There she used EM to study adenovirus transcription. At that time, several pieces of biochemical evidence suggest that the 5’ ends of the late adenovirus mRNAs may not be encoded by DNA sequences contiguous with those encoding the message body. Another investigator at CSHL, Richard Roberts, was convinced by a prevailing hypothesis that the 5’ ends could be derived from an adenovirus-encoded small RNA (the VA RNA) such that parts or all of this small RNA served as a primer for transcription of various late genes. The EM experiments conducted by Dr. Chow were designed to prove this hypothesis. Instead, she observed that adenovirus mRNA created loop structures when hybridized to the adenovirus DNA. This disproved Roberts’ hypothesis and showed that there are coding and non-coding parts of the adenovirus genome leading to the idea of RNA splicing (see below). In 1993, the Nobel Prize in Physiology or Medicine was awarded to Dr. Richard Roberts and Dr. Philip Sharp for the discovery of RNA splicing and split genes. Dr. Chow, despite her EM data being essential for the discovery, was very controversially not included in the prize. While she may not have gotten the Nobel Prize, she continued to revolutionize science with her work on HPV. While at the University of Rochester and University of Alabama at Birmingham, Dr. Chow discovered the purpose of several HPV genes, created the first reproducible tissue culture system for HPV to replicate in the lab, and investigated how HPV causes cancer. Although she is currently retired, Dr. Chow continues to work on identifying drugs to treat HPV infection.
Major Discoveries:
- Discovered split genes and mRNA splicing, which redefined how we view DNA replication
- The genome has parts that are read and parts that are not, when mRNA is processed, the introns or ‘ silent parts’ are cut out
- Described the functions of structure of 2 HPV replication proteins
- Described E1 protein structure and function
- Showed the mechanism that E1 uses to unwind host DNA
- Described E2 protein structure and function
- E2 is the origin recognition protein, regulates transcription, and helps the virus segregate during cell division
- Described E1 protein structure and function
- Created systems to allow HPV to replicate efficiently in the lab
- Created a 3-dimensional organotypic experimental system for HPV culture
- Developed an in-vivo xenograft system to grow HPV
- Elucidated the purpose of HPV protein E7
- Found that E7 takes over the cell cycle and allows the cells to become cancerous
Over 200 Papers Published
- Most cited paper: An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA (1977)
- doi:10.1016/0092-8674(77)90180-5, Cited over 6,000 times
- First 1st author paper: Electron microscope mapping of the distribution of ribosomal genes of the Bacillus subtilis chromosome (1973)
- Most recent paper (as a collaborator): USP16 regulates mitochondrial function by deubiquitinating TOM40, a core component of the translocase in the mitochondrial outer membrane (2026)
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“When you are young, you are not deterred. You don’t even think about how difficult it could be.”
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