mRNA processing, decay and quality control in eukaryotes

Research Seminar
Title: mRNA processing, decay and quality control in eukaryotes
Speaker: Liang Tong, Ph.D.
William R. Kenan, Jr. Professor
Department Chair
Department of Biological Sciences,
Columbia University
Time: 16:00-17:30, Oct. 20, 2017
Location: Youcai Deng Hall，School of Life Sciences（生科院邓祐才报告厅）
Host：Junyu Xiao
Abstract：
mRNA 5`-end capping occurs early during transcription and it was generally believed that the capping process is always successful and no quality control mechanism was known. Our studies have shown that yeast Rai1 and its mammalian homolog DXO are central players in a novel RNA quality surveillance pathway, promoting the degradation of RNAs with incomplete 5`-end capping (1,2). Structures of Rai1 and DXO in complex with various RNA substrates have revealed novel mechanisms for the diverse activity profiles of these enzymes. Most recently, we have shown the existence of NAD-capped RNA in human cells and the deNADding activity of DXO and Rai1 enzymes (3). Overall, these results have opened up a new area of research in RNA biology.
Most eukaryotic mRNA precursors (pre-mRNAs) must undergo extensive processing, which includes 5`-end capping, splicing and 3¢-end cleavage and polyadenylation. Replication-dependent histone pre-mRNAs contain a conserved stem-loop structure near the 3`-end, and they are cleaved but not polyadenylated. Protein machineries with many different factors are required for the 3`-end processing of both types of pre-mRNAs. We have been studying the molecular basis for the functions of these machineries, and have determined the structures of several protein factors and their complexes over the years (4,5). The presentation will also describe recent discoveries from these studies, both by crystallography and by cryo-EM.

Supported by grants from the NIH.

1. Xiang, S., Cooper-Morgan, A., Jiao, X., Kiledjian, M., Manley, J.L., and Tong, L. (2009) Structure and function of the 5`->3` exoribonuclease Rat1 and its activating partner Rai1. Nature 458, 784-788.
2. Jiao, X., Chang, J.H., Kilic, T., Tong, L., and Kiledjian, M. (2013) A mammalian premRNA 5` end capping quality control mechanism and an unexpected link of capping to pre-mRNA processing. Mol. Cell 50, 104-115.
3. Jiao, X., Doamekpor, S.K., Bird, J.G., Nickels, B.E., Tong, L., Hart, R.P., and Kiledjian, M. (2017) 5` end nicotinamide adenine dinucleotide cap in human cells promotes RNA decay through DXO-mediated deNADding. Cell 168, 1015-1027.
4. Mandel, C.R., Kaneko, S., Zhang, H., Gebauer, D., Vethantham, V., Manley, J.L., and Tong, L. (2006) Polyadenylation factor CPSF-73 is the pre-mRNA 3`-end-processing endonuclease. Nature 444, 953-956.
5. Tan, D., Marzluff, W.F., Dominski, Z., and Tong, L. (2013) Structure of histone mRNA stem-loop, human stem-loop binding protein, and 3`hExo ternary complex. Science 339, 318-321.
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