CRCNS: Bioinformatics of Alternative Splicing in the Nervous System

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

EIA-0218506 Burge, Christopher B MIT CRCNS: Bioinformatics of Alternative Splicing in the Nervous System Almost every human cell contains a huge instruction manual called the genome with many thousands of pages (the genes), each of which tells the cell how to make a particular building block (protein) that it needs to live or grow or to perform its assigned function in the body. The cell uses this manual in a complicated way, first copying (transcribing) each page that it needs to a piece of scratch paper (the pre-mRNA), and then cutting and pasting (splicing) pieces of the scratch paper (the exons) together to form the final recipe (mRNA) for the protein product. Interestingly, this cutting and pasting is often carried out in different ways in different types of cells or under different conditions in a process called alternative splicing (AS), generating many different varieties of a protein under different conditions. Alternative splicing is particularly common in neurons, helping to generate protein variants whose properties are optimized to the local environment of the neuron. For example, AS is used to tune the electrical properties of ion channels which help different sensory neurons in the inner ear respond to different frequencies of sound. In addition, mutations that affect AS are associated with a number of neurodegenerative diseases. The goal of the proposal is to gain a better understanding of the signals in a gene that determine how that gene will be spliced when it is expressed in a particular part of the brain, and of how alternative splicing is used to modulate brain function.