mRNA processing, decay and quality control in eukaryotes

Liang Tong, Ph.D.

Professor and Chair

Department of Biological Sciences

1212 Amsterdam Avenue

Columbia University

New York,NY

EXPERIENCE:

September, 1997 — present

Department of Biological Sciences, Columbia University, New York, New York

Professor (July 04–present), Associate Professor (Sept. 97–June 04, tenured July 01)

Chair (July 13-present)

Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut

Principal Scientist (Jan. 96–Aug. 97), Senior Scientist (Aug. 92–Dec. 95)

August, 1989 — July, 1992

Purdue University, West Lafayette, Indiana

Post-Doctoral Research Associate (Prof. Michael G. Rossmann)

August, 1984 — July, 1989

University of California, Berkeley

Graduate Research Assistant (Prof. Sung-Hou Kim)

January, 1983 — July, 1983

Peking University, Beijing, China

Undergraduate Research Assistant (Prof. You-Qi Tang)

Abstract:

Most eukaryotic mRNA precursors (pre-mRNAs) must undergo extensive processing, which includes 5’-end capping, splicing and 3’-end cleavage and polyadenylation. Two distinct machineries, each with a large number of protein factors, are required for 3’-end processing of different types of pre-mRNAs. We have determined the crystal structures of several proteins and sub-complexes in these machineries, which have provided molecular insights into their organization and mechanism of action.

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 of yeast Rai1 and its mammalian homolog Dom3Z (now renamed DXO) revealed that they are novel eukaryotic enzymes with RNA 5’-end pyrophosphohydrolase (PPH) activity as well as decapping activity toward unmethylated caps. These observations led us to demonstrate that RNA 5’-end capping defects exist in yeast and human cells, and that Rai1/DXO are central players in a novel RNA quality surveillance pathway, promoting the degradation of such defective RNAs.

The presentation will also cover our latest discoveries in these and related research areas.

Venue: Room143, New Biology Building, THU

Time: Oct 21 (Monday), 2013; 16:30

Host: Prof. Hongwei Wang