Ataxia-telangiectasia mutated (ATM) mRNA (ATM mRNA)

Ataxia-telangiectasia mutated (ATM) mRNA is the transcript of the ATM gene, which encodes a large serine/threonine kinase that serves as a master regulator of the cellular response to DNA double-strand breaks (Shiloh, Y., 2003). Upon detection of DNA damage, the ATM protein is activated to phosphorylate key substrates like p53 and CHK2, triggering cell cycle arrest, DNA repair, or apoptosis to maintain genomic integrity (UniProt, 2024). Mutations in the ATM gene lead to Ataxia-telangiectasia (A-T), a severe recessive disorder characterized by progressive neurodegeneration, immunodeficiency, and a high risk of lymphoid malignancies (Gatti, R. A., 1991). Targeting ATM mRNA is a specialized therapeutic approach, primarily utilizing antisense oligonucleotides (ASOs) to correct splicing errors in specific A-T mutations, thereby restoring functional protein levels (Cavellan et al., 2016). In the context of oncology, silencing ATM mRNA via RNA interference is being explored as a strategy to sensitize tumor cells to radiotherapy and DNA-damaging chemotherapy by impairing their repair capacity (Sancak, Y. et al., 2021). While small molecule inhibitors of the ATM protein are more common in clinical trials, mRNA-based therapies offer a precision medicine pathway for genetic restoration in A-T patients.

Other names

ATM transcriptAtaxia telangiectasia mutated mRNASerine/threonine-protein kinase ATM mRNA

Splice-switching to restore functional protein expression or RNA interference-mediated knockdown to sensitize cells to DNA damage.