Autophagy-related gene messenger RNA (ATG mRNA)

Autophagy-related gene (ATG) messenger RNAs are the transcript products of a conserved set of genes that regulate the process of macroautophagy, a lysosomal degradation pathway essential for maintaining cellular homeostasis (Klionsky, D. J., et al., Developmental Cell, 2003). These mRNAs encode proteins that form functional complexes, such as the ULK1 initiation complex and the ATG12-ATG5-ATG16L1 conjugation system, which are vital for the nucleation and expansion of the autophagosome (Mizushima, N., & Komatsu, M., Cell, 2011). In the context of disease, ATG mRNAs are often dysregulated; for instance, their upregulation in certain cancers can promote tumor survival and resistance to chemotherapy by providing nutrients under metabolic stress (Galluzzi, L., et al., EMBO Journal, 2017). Conversely, impaired expression of these transcripts is linked to the accumulation of toxic protein aggregates in neurodegenerative disorders like Alzheimer's and Parkinson's disease (He, C., & Klionsky, D. J., Annual Review of Genetics, 2009). Therapeutic strategies targeting these mRNAs primarily utilize RNA interference (RNAi) or antisense oligonucleotides (ASOs) to either silence pro-survival autophagy in tumors or potentially modulate autophagic flux in other pathological states (Levine, B., & Kroemer, G., Cell, 2019). While promising, targeting these transcripts poses challenges, including the risk of disrupting basal autophagy, which is necessary for the survival of healthy non-target cells (Mizushima, N., & Komatsu, M., Nature, 2008).

Other names

ATG gene transcriptsAutophagy-related transcriptsMacroautophagy-related mRNAsATG gene products

RNA interference (RNAi) or antisense-mediated degradation (RNase H-dependent) of mRNA transcripts to prevent the translation of proteins essential for autophagosome formation and maturation (Levine, B., & Kroemer, G., Cell, 2019).