The Impact of RNA processing on Human Neurodegenerative Diseases (ALS)
As an undergraduate researcher in the Yeo Lab, I am currently studying the impact of RNA processing and the types of regulation that generates neurodegenerative diseases which occurs on the human gene. Majority of the time RNA sequences are always associated with RNA binding proteins (RBPs). RBPs recognize and bind to RNA elements within pre-mRNA sequence to form mRNA-protein (mRNP) complexes which regulates targeted RNAs.
The RBPs identify the RNA elements which control the functions and structures of the target RNA which constitute the mRNP code. This code is the basis for many human diseases; thus, any disruption in the code due to mutations in the RBPs or the RNA elements would result in abnormal phenotypes and neurodegenerative diseases such as ALS.
The RNA elements control the stability of RNA and regulate the process of translation of mRNA (messenger RNA is transcribed from DNA and serves as a blueprint in the synthesis of proteins). These elements either enhance or silence (or prevent) the process of converting the premature mRNA to the mature mRNA.
A recently study of 323 mouse RBPs via in situ hybridization, revealed that two-thirds of the RBPs studied were expressed in the brain. This study implies that neurons depend heavily on RBPs to function properly. In the nervous system, the binding of RBPs to the mRNA acts as a shield which protects the mRNA to properly synthesize proteins. RBPs that ensure the stability of the mRNA play an important role in the process of learning and memory. This suggests that RBPs are the building blocks in maintaining balance and stability in the nervous system.
In order to develop a realistic and effective disease models for ALS, is it crucial to acquire an understand of how RBPs control RNA processing. The first step is to discover the various binding activities between RNA elements and RBPs. The second step is to understand the mRNP codes that corresponds to differentiation, development, and survival of neural stem cells. The information acquired from these first two steps will provide the necessary information in order to relate the defects in RNA processing to neurodegenerative diseases like ALS. By grasping the knowledge of the causes of neurodegenerative diseases at a microscopic level, the pharmaceutical industry can utilize this information to develop medication to find a cure for these neurodegenerative diseases.