Ataxia telangiectasia and Rad3-related protein mRNA (ATR mRNA) (ATR mRNA)

Ataxia telangiectasia and Rad3-related (ATR) mRNA is the messenger RNA transcript that encodes the ATR protein, a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family. The ATR protein is a central coordinator of the DNA damage response (DDR), specifically sensing replication stress and single-stranded DNA (ssDNA) gaps that occur at stalled replication forks [UniProt Q13535, PubMed 12676583]. Upon activation, ATR phosphorylates downstream targets like CHK1 to induce cell cycle arrest, stabilize replication forks, and promote DNA repair [PubMed 11533492]. Targeting ATR mRNA using RNA interference (RNAi) or antisense oligonucleotides (ASOs) aims to silence the expression of the ATR protein, thereby compromising the cell's ability to manage replication stress. This strategy is particularly effective in cancer cells that already possess defects in other DDR pathways, such as ATM loss, creating a state of synthetic lethality [PubMed 15448698]. While most clinical-stage ATR inhibitors are small molecules that target the protein's kinase activity, the mRNA remains a target for experimental gene-silencing therapies designed to sensitize tumors to chemotherapy and radiation. Key challenges in targeting ATR mRNA include ensuring tumor-specific delivery and managing toxicities like myelosuppression, which arise from the inhibition of ATR in rapidly dividing healthy tissues [PubMed 24301968].

Other names

ATRMEC1SCKLSCKL1FRP1FRAP-related protein 1 mRNA

Degradation of ATR mRNA via RNA interference (RNAi) or antisense-mediated RNase H cleavage, resulting in the depletion of ATR protein and subsequent inhibition of the DNA damage response pathway [PubMed 11533492, PubMed 12676583].