Deciphering the splicing order of COL6A1-3 pre-mRNAs to improve the prognosis and treatment of collagen VI-related muscular dystrophies
Awardee: Karine Choquet
Institution: Université de Sherbrooke
Grant Amount: $46,611
Funding Period: February 1, 2025 - January 31, 2026
Summary:
Collagen VI-related muscular dystrophies (COL6-RD) are a rare type of childhood-onset muscle disease. Symptoms include muscle weakness and breathing difficulties. There is currently no cure for COL6-RD, which are caused by spelling errors in the genes COL6A1, COL6A2 and COL6A3. These errors are also present in the COL6 premature (pre) messenger RNAs (mRNA), which must undergo a process called splicing to become the mature mRNAs that are used to produce collagen proteins. Some of the spelling errors that cause COL6-RD lead to defects in splicing. Depending on the type of splicing defect, the disease symptoms can be milder or more severe. The type of splicing defect can also determine which type of treatment could be beneficial. However, predicting the type of splicing defect can be challenging. COL6 pre-mRNAs are very long, but splicing has only been studied for one short section of a pre-mRNA at a time. Our project will use new technology that allows to read much longer sections of COL6 pre-mRNAs. We will investigate the order in which splicing happens in the COL6 pre-mRNAs, and how this influences the type of splicing defect caused by genetic spelling errors. We will also study how communication between different parts of a pre-mRNA that are located far away from one another affects the efficiency of treatments that aim to correct COL6 splicing defects. This project will improve our understanding of how splicing goes wrong in COL6-RD and could lead to improved treatment options for some of the spelling errors that cause COL6-RD.