Ataxia-telangiectasia mutated precursor messenger RNA (ATM pre-mRNA) (ATM pre-mRNA)

Ataxia-telangiectasia mutated (ATM) pre-mRNA is the primary transcript of the ATM gene, which encodes a critical serine/threonine kinase responsible for orchestrating the cellular response to DNA double-strand breaks [UniProt]. The ATM protein functions as a master regulator of the DNA damage response (DDR), activating downstream targets involved in cell cycle checkpoints, DNA repair, and apoptosis [Nature Reviews Cancer]. Mutations in the ATM gene that disrupt the processing of its pre-mRNA, such as deep intronic mutations leading to pseudoexon inclusion, result in the loss of functional ATM protein and cause the multi-system disorder Ataxia-telangiectasia (A-T) [PubMed]. A-T is characterized by progressive neurodegeneration, particularly cerebellar ataxia, as well as immunodeficiency and a high predisposition to lymphoid malignancies [NIH]. ATM pre-mRNA has emerged as a therapeutic target for antisense oligonucleotides (ASOs) designed to modulate splicing and restore the production of full-length, functional ATM protein [Molecular Therapy]. These splice-switching therapies aim to bypass specific genetic defects by excluding aberrant exons or correcting splice site selection, offering a potential precision medicine approach for A-T patients with specific genotypes [PubMed].

Other names

ATM transcriptATM precursor mRNAAtaxia-telangiectasia mutated transcript

Splice-switching to correct aberrant splicing or exclude pseudoexons, thereby restoring functional protein expression.