The work: Messenger RNA (mRNA) takes genetic instructions from DNA and uses them to create proteins that carry out multiple cellular functions. Dr. Maquat discovered nonsense- mediated mRNA decay (NMD) in human cells. NMD is a quality control mechanism that removes flawed messenger RNA molecules that, if left intact, would lead to the production of abnormal proteins that could be toxic to cells and initiate disease. Cells also use this pathway to better respond to changing environmental conditions. For example, breast cancer cells inhibit this pathway to augment their response to chemotherapy and hasten cell death.
The impact: Nonsense-mediated mRNA decay functions in one-third of inherited disorders, such as cystic fibrosis, and one-third of acquired diseases, including many forms of cancer. Her work has furthered our understanding of the molecular basis of human disease and provides valuable information to help physicians implement “personalized” or “precision” medicine by treating the disease mutation that is specific to each individual patient.
Lynne E. Maquat holds the J. Lowell Orbison Endowed Chair and is Professor of Biochemistry & Biophysics and Professor of Oncology in the School of Medicine and Dentistry, Director of the Center for RNA Biology: From Genome to Therapeutics, and Chair of Graduate Women in Science at the University of Rochester in Rochester, New York, USA. After obtaining her PhD from the University of Wisconsin-Madison and post-doctoral work at the McArdle Laboratory for Cancer Research in Madison, she joined the Roswell Park Cancer Institute in Buffalo before moving her laboratory to the University of Rochester. Professor Maquat is known for her mammalian-cells studies of nonsense-mediated messenger RNA decay, which she first reported in 1981 through studies of the hemolytic anemia bo-thalassemia and from which she subsequently discovered the pioneer round of translation, the exon-junction complex (EJC), and how the EJC marks mRNAs for a first quality-control translation cycle that largely occurs as newly synthesized messenger RNAs enter the cytoplasm. She continues to make seminal contributions on mechanisms of NMD and another pathway she discovered and named Staufen-mediated mRNA decay (SMD). Her work on SMD has defined new roles for long non-coding RNAs and small interspersed elements in humans and rodents, unveiling the complexities of RNA-RNA interactions that comprise important post-transcriptional gene regulatory pathways during mammalian-cell development and differentiation. Professor Maquat has served on editorial boards including RNA, Mol. Cell Biol., RNA Biol., and Methods, as an elected Director, Treasurer/Secretary and President of the RNA Society, as a member of the Public Information Committee of the American Society for Cell Biology, and as chair of NIH study section. She is an elected Fellow of the American Association for the Advancement of Science (2006), an elected Member of the American Academy of Arts and Sciences (2006) and the National Academy of Sciences (2011), and a Batsheva de Rothschild Fellow of the Israel Academy of Sciences and Humanities (2012). Professor Maquat was awarded the William C. Rose Award from the American Society for Biochemistry and Molecular Biology (2014) for research and mentoring, in particular advocacy for women in science.