Non-telomeric role for Rap1 in regulating metabolism and protecting against obesity

The mammalian telomere-binding protein Rap1 was found to have additional non-telomeric functions, acting as a transcriptional cofactor and a regulator of the NF-kB pathway. Here, we assess the effect of disrupting mouse Rap1 in vivo, and report on its unanticipated role in metabolic regulation and body weight homeostasis. Rap1 inhibition causes dysregulation in hepatic as well as adipose function. In addition, using a separation-of-function allele, we show that the metabolic function of Rap1 is independent of its recruitment to TTAGGG binding elements found at telomeres, and at other interstitial loci.

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Yeung F, Ramírez CM, Mateos-Gomez PA, Pinzaru A, Ceccarini G, Kabir S, Fernández-Hernando C, Sfeir A