Life Sciences & Biotechnology
Title : | Cerebellar ataxia (CANVAS) associated AAGGG repeats in RFC1 gene promote the formation of G-quadruplex structure leading to proteinopathy |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Prof. Amit Kumar, Indian Institute Of Technology (IIT) Indore, Madhya Pradesh |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | amitk@iiti.ac.in |
Equipments : | Verticle Gel Electrophoresis |
Details
Executive Summary : | Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome (CANVAS) is a genetic disorder characterized by the RFC1 genetic expansion of the (AAGGG)n tandem sequence. It affects about one in 3,000 neurological patients. CANVAS was first identified in 2004 and has not been studied extensively. Pathogenic repeat expansions are linked to the retention of repeat-hosting introns in guanine-cytosine rich intronic expansions of (CCGGGG)n, such as C9orf72-amyotrophic lateral sclerosis/FTD (ALS), which form G-quadruplex structures. To understand the molecular mechanism of late-onset ataxia and CANVAS, researchers hypothesize that non-canonical G-quadruplex structures are formed in the (AAGGG)exp, which has been observed to form stable G-quadruplex structures. This structure could bind with several splicing regulators, leading to RNA gain of function. RNA gain of function is a primary cause of toxicity in G-quadruplex-mediated neuropathies like ALS. A CANVAS patient-derived cell line will be used to study the molecular mechanism of the disease, and structural studies will be conducted to obtain a three-dimensional structure for the complex formed between protein and the pathogenic repeat sequence RNA of the CANVAS. |
Total Budget (INR): | 60,45,285 |
Organizations involved