Larp7, short for La ribonucleoprotein domain family member 7, is a master regulator involved in multiple essential biological functions. It is associated with pathways such as the DNA damage response and RNAPII pausing. Larp7 also binds to 7SK RNA as part of a 7SK small nuclear ribonucleoprotein, which inhibits the transcriptional activity of RNA polymerase II. It is also implicated in the assembly, modification, processing and cellular transport of RNA molecules [3].

Global and cardiac-specific Larp7 knockout (KO) mouse models have been crucial in revealing its functions. Constitutive Larp7 KO in mice leads to impaired mitochondrial biogenesis, myocardial hypoplasia, and mid-gestational lethality. Cardiac-specific inactivation results in defective mitochondrial biogenesis, impaired oxidative phosphorylation, elevated oxidative stress, and heart failure (HF) by 4 months of age. These occur due to reduced SIRT1 stability and deacetylase activity, which impairs SIRT1-mediated transcription of genes for oxidative phosphorylation and energy metabolism [1]. Deletion of Larp7 in a rodent model also leads to senescent cell accumulation and premature aging, accelerating cellular senescence through the ATM-LARP7-SIRT1-p53/p65 axis [2].

In conclusion, Larp7 is essential for mitochondrial biogenesis, energy production, and cardiac function, and its reduction contributes to HF pathogenesis. Larp7 also plays a key role in cellular senescence and aging. The KO and conditional knockout (CKO) mouse models have been instrumental in understanding Larp7's role in heart failure and cellular senescence-related diseases, providing potential therapeutic targets for these conditions.