Larp1-flox Mouse

Larp1, or La-related protein 1, is an RNA-binding protein belonging to the LARP superfamily. It is crucial for post-transcriptional regulation, controlling the translation and stability of mRNAs, especially those with a 5' terminal oligopyrimidine (5'TOP) motif, which encode ribosomal proteins and translation factors. Larp1 is involved in the mTOR signalling cascade, integrating nutrient sensing with mRNA translation [1,2]. It also has a role in processes like gametogenesis, embryogenesis, sex determination, and cell division in animals, as well as acclimation to stress in yeasts and plants [3].

In humans, Larp1 haploinsufficiency, caused by de novo heterozygous loss-of-function or missense variants in the LARP1 gene, is associated with an autosomal dominant neurodevelopmental disorder. Lymphocytes from a proband with a truncating variant in one allele of LARP1 showed reduced rates of aerobic respiration and glycolysis, suggesting that lower Larp1 levels lead to attenuated metabolic activity in the developing fetal brain [4]. In hepatoblastoma, upregulated O-GlcNAcylated Larp1, mediated by circCLNS1A, promotes tumorigenesis and progression through the Larp1/DKK4/β-catenin axis [5].

In conclusion, Larp1 is a key mRNA-binding protein involved in multiple biological processes and diseases. Its role in translational regulation of TOP mRNAs and in processes like cell division and proliferation is well-established. Studies on Larp1, especially through loss-of-function models in humans, have revealed its significance in neurodevelopmental disorders and cancer, providing insights into potential therapeutic targets for these conditions.