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Isoleucyl-tRNA synthetase 1 (IARS1) mRNA is the transcript encoding the cytoplasmic enzyme responsible for catalyzing the attachment of isoleucine to its corresponding tRNA molecule, a critical step in protein synthesis (UniProt, P41252). Beyond its primary role in translation, IARS1 is a component of the multi-tRNA synthetase complex (MSC), which regulates various cellular processes including signaling and immune responses (NCBI Gene ID: 3376). In the context of oncology, IARS1 mRNA is frequently overexpressed in several malignancies, such as lung and gastric cancers, where it promotes cell proliferation and survival (Huang et al., 2019). Consequently, the mRNA itself has emerged as a potential therapeutic target for RNA-based interventions, including small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs), aimed at downregulating protein expression to inhibit tumor growth (PubMed: 31485715). Mutations in the IARS1 gene are also associated with GRID syndrome, a rare multisystem disorder characterized by growth retardation, intellectual disability, and hepatopathy (Kopajtich et al., 2016). Therapeutic strategies targeting this mRNA seek to exploit the dependency of cancer cells on high levels of protein synthesis machinery. However, challenges remain regarding the efficient delivery of these nucleic acid therapies to target tissues and the potential for off-target effects.
Targeting of the mRNA transcript via RNA interference (siRNA) or RNase H-mediated cleavage (ASOs) to prevent the translation of the IARS1 protein.
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