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

Global and cardiac-specific Larp7 knockout (KO) mouse models have been crucial in understanding its function. 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 by 4 months of age. These effects are accompanied by reduced SIRT1 stability and deacetylase activity, which impairs SIRT1-mediated transcription of genes for oxidative phosphorylation and energy metabolism, dampening cardiac function. In a mouse model of myocardial infarction, restoring Larp7 expression improves the function of the injured heart. Also, deletion of Larp7 in a rodent model leads to senescent cell accumulation and premature aging, accelerating cellular senescence [1,2].

In conclusion, Larp7 is essential for mitochondrial biogenesis, energy production, and cardiac function by modulating SIRT1 homeostasis and activity. Mouse KO models have revealed its significance in heart failure pathogenesis. Additionally, Larp7 plays a role in preventing cellular senescence and aging. Understanding Larp7's functions through these models provides potential therapeutic targets for heart-related diseases and age-associated conditions.