Abstract
Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-living rodent species. A reason for their long lifespan is pronounced cancer resistance. Therefore, researchers believe that NMRs have unknown secrets of cancer resistance and seek to find them. Here, to reveal the secrets, we noticed a retrotransposon, long interspersed nuclear element 1 (L1). L1s can amplify themselves and are considered endogenous oncogenic mutagens. Since the NMR genome contains fewer L1-derived sequences than other mammalian genomes, we reasoned that the retrotransposition activity of L1s in the NMR genome is lower than those in other mammalian genomes. In this study, we successfully cloned an intact L1 from the NMR genome and named it NMR-L1. An L1 retrotransposition assay using the NMR-L1 reporter revealed that NMR-L1 was active retrotransposon, but its activity was lower than that of human and mouse L1s. Despite lower retrotrasposition activity, NMR-L1 was still capable of inducing cell senescence, a tumor-protective system. NMR-L1 required the 3′ untranslated region (UTR) for retrotransposition, suggesting that NMR-L1 is a stringent-type of L1. We also confirmed the 5′ UTR promoter activity of NMR-L1. Finally, we identified the G-quadruplex structure of the 3′ UTR, which modulated the retrotransposition activity of NMR-L1. Taken together, the data indicate that NMR-L1 retrotranspose less efficiently, which may contribute to the cancer resistance of NMRs.
Highlights
Naked mole-rats (NMRs; Heterocephalus glaber) are mouse-sized and the longest-living rodents d iscovered[1]
All the residues we compared were conserved in the NMR-L1 ORF1p and ORF2p (Fig. 1, B and C)
Previous studies have proposed several possible reasons for this resistance, including a highly efficient surveillance system of cell cycles and resistance to multiple stressors[5,26]. We reasoned that such secrets likely include low retrotransposition activity since the NMR genome contains fewer retrotransposons than other mammalian g enomes[7]
Summary
Naked mole-rats (NMRs; Heterocephalus glaber) are mouse-sized and the longest-living rodents d iscovered[1]. Activation of the tumor suppressor ARF and the disruption of oncogenic ERAS can exhibit tumor resistance in NMR-induced pluripotent stem cells[6] Another feature of NMRs that may be related to cancer resistance is fewer transposon-derived sequences than found in other mammals (25% in the NMR, 41% in the human, 38% in the mouse and 36% in the rat genomes)[7]. Transposons, such as endogenous retroviruses (ERVs) and long interspersed elements (LINEs), can autonomously amplify themselves in the g enome[8], which may produce oncogenic mutations and/or induce genomic instability, thereby promoting cancer d evelopment[9,10,11,12,13]. We cloned an active L1 from the NMR genome and characterized it to evaluate our hypothesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
