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Liang Tong

chinese academy of sciences
H指数:91
被引数:2.6万

个人简介

A major focus of our research is on proteins involved in pre-mRNA and non-coding RNA 3'-end processing. Most eukaryotic mRNA precursors must undergo cleavage and polyadenylation in their 3'-ends before they can function as mRNAs. This 1.6 MDa canonical processing machinery contains more than 16 protein factors. Replication-dependent histone pre-mRNAs are cleaved at their 3'-ends but not polyadenylated, and a distinct machinery, U7 snRNP (1 MDa), is required for this processing. Integrator (17 subunits, 1.6 MDa) is involved in non-coding RNA 3'-end processing and attenuation of pre-mRNA expression through promoter-proximal transcription termination of RNA polymerase II. The goal of our research is to understand the molecular basis of these important cellular events. We will produce structures of the protein subunits, protein-protein and protein-RNA sub-complexes, and the entire machinery, and carry out functional studies to assess the structural information. Our recent studies unexpectedly led to the identification of an mRNA 5'-end capping quality control mechanism. We have identified the enzymes (Rai1, Dxo1, DXO) that play a central role in this mechanism. We are characterizing their biochemical properties and deciphering their physiological functions in yeast as well as mammalian cells. Another area of our research is on enzymes that are involved in fatty acid and/or carbohydrate metabolism. These include acetyl-coenzyme A carboxylase (ACC), carnitine acyltransferase, AMP-activated protein kinase (AMPK), ATP-citrate lyase (ACLY) and others. These enzymes are important targets for drug discovery against obesity, diabetes and other human diseases. The goals of our research are to produce structural information on these enzymes and to understand their functions at the molecular level. The structural information will also lay the foundation for drug discovery against these targets.

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