生命科学联合中心学术报告

题目：Neuronal Mechanisms and Programs Regulating Alternative Pre-mRNA Splicing

报告人：Douglas L. Black, Ph.D.

Professor, Howard Hughes Medical Institute, UCLA

时间：2015-4-16（周四），15:00-16:15pm

地点：北京大学邓祐才报告厅

联系人：伊成器

Our lab works on a range of projects related to the control of pre-mRNA splicing in neurons. We aim to determine the mechanisms of action of splicing regulators, as well as to understand their roles in neural development and mature neuronal function. We have long-standing projects focused on two families of regulatory factors: the polypyrimidine tract–binding proteins (PTBP1 and PTBP2), and the Rbfox proteins (1, 2 and 3). Each of these RNA binding proteins alters the splicing of a specific set of gene transcripts in neurons, and each can induce different splicing outcomes depending on the position of its binding relative to a target exon. The PTB proteins control transitions in splicing regulation that occur during early and late neuronal differentiation, and are required for proper neuronal maturation and synaptogenesis. The Rbfox proteins control the isoform choice of many synaptic proteins determining neuronal activity in mature cells, such as ion channels, neurotransmitter receptors, and proteins involved in calcium signaling. In mechanistic studies, we use biochemical methods and in vitro splicing systems to examine the molecular interactions of these proteins and analyze how they can alter spliceosome assembly. In other efforts, we use whole transcriptome sequencing, ES and primary neuronal cell culture models, and conditional knockout mice to understand how these proteins, and their particular splicing targets, affect neuronal development and activity.

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