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Significance LINE-1 retrotransposons are mobile genetic elements that have significantly contributed to the evolution of our genome. However, unhindered LINE-1 mobility can be detrimental and cause various genetic disorders. Here, we identify the antiviral protein TRIM5α as host factor that controls LINE-1 elements and protects our genome from novel insertions. In addition, we show that TRIM5α recognizes LINE-1 ribonucleoprotein complexes as a molecular pattern and initiates innate immune signaling upon sensing. Thus, our findings confirm the role of TRIM5α as pattern recognition receptor in innate immunity and uncover its important role in safeguarding the genome against endogenous mobile genetic elements.

Human TRIM5α senses and restricts LINE-1 elements