James L Manley

James Manley, PhD, is Julian Clarence Levi Professor of Life Sciences at Columbia University, where his laboratory studies gene expression in mammalian cells. Manley and colleagues identified and characterized the key factors responsible for polyadenylation of mRNA precursors, and elucidated how this remarkably complex machinery functions in gene regulation, for example during cell growth and differentiation. He has also studied the mechanism and regulation of the process by which introns are removed from mRNA precursors, mRNA splicing. Manley and his coworkers codiscovered the first alternative splicing factor (SR protein), characterized how this and other splicing regulatory proteins function and are themselves regulated, showed how alternative splicing can become deregulated in disease, and with respect to mechanism demonstrated that two spliceosomal small nuclear RNAs by themselves have catalytic activity. Finally, he elucidated unexpected links between these mRNA processing reactions and transcription, DNA damage signaling and maintenance of genomic stability. His work has thus provided considerable insight into the complex mechanisms that are essential for the regulated production of mRNAs in mammalian cells.