Lynne Maquat, Ph.D., the founding director of the Center for RNA Biology at the University of Rochester, has been awarded the Warren Alpert Foundation Prize for her pivotal discoveries in the field of RNA biology. She shares the prize with fellow RNA biologist Joan Steitz, Ph.D., Sterling Professor of Molecular Biophysics and Biochemistry at Yale School of Medicine.
The award is given by the Warren Alpert Foundation in recognition of work that has improved the understanding, prevention, treatment or cure of human disease. The prize is administered by Harvard Medical School, and since its inception in 1987, 12 honorees have gone on to receive Nobel prizes.
George Q. Daley, dean of Harvard Medical School, said of Maquat and Steitz: “The discoveries made by the two award winners are stunning in their elegance and scope.” Earlier this year, the pair won the 2021 Wolf Prize in Medicine for their work. They shared the Wolf Prize with a third RNA biologist, Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory.
RNA Makes its Mark
Maquat has studied RNA since she started her own laboratory in 1982. But until the development and approval of multiple mRNA COVID-19 vaccines in 2020, RNA wasn’t on the public radar. Decades of research by Maquat and Steitz on how RNAs work and how they are involved in human disease helped set the stage for the rapid development of these vaccines, which are key to bringing the COVID pandemic under control.
Many are familiar with DNA, which contains the genetic instructions that make us who we are. But RNA is equally important in the process of gene expression:
- DNA lives in the nucleus of a cell and makes many types of RNA, including mRNA (messenger RNA).
- mRNA takes genetic instructions from DNA, travels out of the nucleus and delivers them to factories in our cells called ribosomes.
- Ribosomes use the instructions to create proteins.
- Proteins carry out myriad functions throughout the body, including ferrying nutrients around, helping with chemical reactions and protecting us from disease.
Maquat: Honors & Awards
Warren Alpert Foundation Prize
Wolf Prize in Medicine
Wiley Prize in Biomedical Sciences
Vanderbilt Prize in Biomedical Science
Lifetime Achievement Award in Science, RNA Society
Elected to National Academy of Medicine
FASEB Excellence in Science Award
Canada Gairdner International Award
(First winner from Upstate New York)
Elected to National Academy of Sciences
Lifetime Achievement Award in Service, RNA Society
Elected to American Academy of Arts and Sciences
Many disorders result from problems with our DNA, but over the past several decades Maquat, Steitz and other scientists revealed that mRNA plays a role in a multitude of diseases, too. Cystic fibrosis, fragile X syndrome, Duchene muscular dystrophy and a long list of other inherited and acquired diseases result from defective mRNAs.
“Scientists used to think that gene regulation was all about DNA, and that RNA didn’t influence gene expression, the production of proteins or the development of disease,” said Maquat, the J. Lowell Orbison Endowed Chair and Professor of Biochemistry and Biophysics, Oncology and Pediatrics at the University of Rochester School of Medicine and Dentistry. “We now know that a very complicated network exists in our cells to regulate how, when and where our mRNAs are produced. This knowledge has opened the door to using RNA as both a treatment target and a tool to develop new therapies.”
The Importance of Quality Control
Maquat is best known for discovering a mechanism that destroys faulty mRNAs in human cells. Called nonsense-mediated mRNA decay (NMD), this mechanism acts as a quality control system that is important in both health and disease.
The “nonsense” in nonsense-mediated mRNA decay refers to an early stop signal called a “nonsense codon.” Normally, stop signals (called termination codons) appear at the end of the genetic instructions in mRNA. The stop signal indicates that the instructions have been read start-to-finish and that all of the information has been translated into a full-length and functional protein.
Unlike termination codons, nonsense codons appear somewhere in the middle of the genetic instructions in mRNA; this early stop signal prevents the instructions from being read completely. Consequently, protein synthesis is cut short. Similar to installing a sink with only half of the instructions, or baking a cake with half of a recipe, nonsense codons lead to undesired results: a protein might not be produced at all, or a truncated protein may be produced, either of which can cause disease.
Here’s how NMD works:
- The genetic instructions in DNA are transcribed into mRNA.
- The mRNA makes its way from the nucleus to the cytoplasm where ribosomes inspect it for a nonsense codon (early stop signal). This signal will prevent the genetic instructions from being read completely, barring the formation of a full-length and functional protein.
- If a nonsense codon is detected, the mRNA is flagged and destroyed, averting the creation of a shortened, potentially disease-causing protein.
- If there is no nonsense codon, the mRNA will deliver the genetic information to lots of ribosomes and the correct amount of normal protein will be made.
Maquat and Steitz will be recognized at a virtual scientific symposium on Oct. 7 hosted by Harvard Medical School. For further information, visit the Warren Alpert Foundation Prize symposium web site.