Delineating the Structural Blueprint of the Pre-mRNA 3′-End Processing Machinery

Abstract

Processing of mRNA precursors (pre-mRNAs) by polyadenylation is an essential step in gene expression. Polyadenylation consists of two steps, cleavage and poly(A) synthesis, and requires multiple cis elements in the pre-mRNA and a megadalton protein complex bearing the two essential enzymatic activities. While genetic and biochemical studies remain the major approaches in characterizing these factors, structural biology has emerged during the past decade to help understand the molecular assembly and mechanistic details of the process. With structural information about more proteins and higher-order complexes becoming available, we are coming closer to obtaining a structural blueprint of the polyadenylation machinery that explains both how this complex functions and how it is regulated and connected to other cellular processes.

ACKNOWLEDGMENTS

Kehui Xiang was a joint student in the Tong and Manley laboratories.

The research from our labs described here was supported by grants from the NIH to L.T. (GM077175) and J.L.M. (GM28983).

Additional information

Notes on contributors

Kehui Xiang

Kehui Xiang received his B.S. from Tsinghua University in China, majoring in mathematics and physics. He was awarded a faculty fellowship to pursue his graduate study at Columbia University in 2007. Comentored by Liang Tong and James L. Manley, he studied protein factors involved in eukaryotic mRNA 3′ processing by using crystallography and biochemistry. His research has been published in several peer-reviewed journals, such as Nature, Nature Communications, and Genes & Development. He received the Peter Sajovic Memorial Prize for outstanding work in biology and his Ph.D. in 2013 at Columbia University. Dr. Xiang is now a postdoctoral associate in David Bartel's lab at the Whitehead Institute, Massachusetts Institute of Technology.

Liang Tong

Liang Tong is currently professor and chair of the Department of Biological Sciences at Columbia University in New York City. He received his Ph.D. in 1989 from the University of California at Berkeley and did his postdoctoral research at Purdue University. In 1992, he became a senior scientist (and in 1996 the principal scientist) at Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT. He is the recipient of the first Boehringer Ingelheim (Worldwide) Research and Development Award. He became an associate professor at Columbia University in 1997 and a professor in 2004. He has published more than 220 papers, and his research focuses on structural and functional studies of proteins involved in mRNA processing and enzymes involved in fatty acid metabolism. He was elected a fellow of the American Association for the Advancement of Science in 2009.

James L. Manley

James L. Manley received a B.S. from Columbia University and a Ph.D. from Stony Brook/Cold Spring Harbor Laboratory and did postdoctoral work at the Massachusetts Institute of Technology. He has been in the Department of Biological Sciences at Columbia University since 1980 and was chair from 1995 to 2001 and Julian Clarence Levi professor of life sciences since 1995. His research interests center on understanding the mechanisms and regulation of gene expression in mammalian cells. His work has been supported by many grants, including an NIH MERIT Award. He has authored or coauthored over 300 research articles and reviews on these topics and is an ISI Highly Cited Researcher. Dr. Manley is or has been an editor of three journals and has served on numerous editorial boards and review panels. He is a fellow of the American Academy of Microbiology, the American Academy of Arts and Sciences, and the American Association for the Advancement of Science and a member of the National Academy of Sciences.