RNA-Binding Proteins and the Complex Pathophysiology of ALS

• Main Authors: Wanil Kim, Do-Yeon Kim, Kyung-Ha Lee
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: International Journal of Molecular Sciences
• Subjects: ALS; RNA-binding protein; membrane-less organelles
• Online Access: https://www.mdpi.com/1422-0067/22/5/2598

Genetic analyses of patients with amyotrophic lateral sclerosis (ALS) have identified disease-causing mutations and accelerated the unveiling of complex molecular pathogenic mechanisms, which may be important for understanding the disease and developing therapeutic strategies. Many disease-related genes encode RNA-binding proteins, and most of the disease-causing RNA or proteins encoded by these genes form aggregates and disrupt cellular function related to RNA metabolism. Disease-related RNA or proteins interact or sequester other RNA-binding proteins. Eventually, many disease-causing mutations lead to the dysregulation of nucleocytoplasmic shuttling, the dysfunction of stress granules, and the altered dynamic function of the nucleolus as well as other membrane-less organelles. As RNA-binding proteins are usually components of several RNA-binding protein complexes that have other roles, the dysregulation of RNA-binding proteins tends to cause diverse forms of cellular dysfunction. Therefore, understanding the role of RNA-binding proteins will help elucidate the complex pathophysiology of ALS. Here, we summarize the current knowledge regarding the function of disease-associated RNA-binding proteins and their role in the dysfunction of membrane-less organelles.