The Relationship Between Sen1 and Amyotrophic Lateral Scelerosis: The Devil Lies in the Details
Abstract
In the cell, DNA is transcribed into RNA and RNA is translated into proteins. When RNA is being transcribed by the RNA polymerase, specific termination signals exist to define the length and the composition of the encoded message in the RNA. The accurate termination of transcription is essential for the creation of functional RNAs and improper termination produces translated proteins with aberrant functions that can result in disease states. Sen1 is a superfamily I helicase found in Saccharomyces cerevisiae (baker's yeast). Sen1 and its human homolog, Senataxin, are proteins that have important roles in transcription termination; however, the mechanism of termination and the precise role these proteins play has remained elusive. Mutations in Senataxin resulting in improper transcription termination have been implicated in Amyotrophic Lateral Sclerosis Type 4 (ALS4) and Ataxia with Oculomotor Apraxia Type 2 (AOA2). Given their highly conserved sequence and function homologies, elucidations of Sen1's role in transcription termination can be inferred to Senataxin. Our goal is a detailed characterization of Sen1 and an understanding of its precise role in transcription termination. We have biochemically purified the Sen1 protein and show that it can bind to DNA and RNA, and that it uses ATP to move on nucleic acids.
The Relationship Between Sen1 and Amyotrophic Lateral Scelerosis: The Devil Lies in the Details
In the cell, DNA is transcribed into RNA and RNA is translated into proteins. When RNA is being transcribed by the RNA polymerase, specific termination signals exist to define the length and the composition of the encoded message in the RNA. The accurate termination of transcription is essential for the creation of functional RNAs and improper termination produces translated proteins with aberrant functions that can result in disease states. Sen1 is a superfamily I helicase found in Saccharomyces cerevisiae (baker's yeast). Sen1 and its human homolog, Senataxin, are proteins that have important roles in transcription termination; however, the mechanism of termination and the precise role these proteins play has remained elusive. Mutations in Senataxin resulting in improper transcription termination have been implicated in Amyotrophic Lateral Sclerosis Type 4 (ALS4) and Ataxia with Oculomotor Apraxia Type 2 (AOA2). Given their highly conserved sequence and function homologies, elucidations of Sen1's role in transcription termination can be inferred to Senataxin. Our goal is a detailed characterization of Sen1 and an understanding of its precise role in transcription termination. We have biochemically purified the Sen1 protein and show that it can bind to DNA and RNA, and that it uses ATP to move on nucleic acids.