MOV10 recruits DCP2 to decap human LINE ‐1 RNA by forming large cytoplasmic granules with phase separation properties

Abstract

Long interspersed element 1 (LINE‐1) is the only active autonomous mobile element in the human genome. Its transposition can exert deleterious effects on the structure and function of the host genome and cause sporadic genetic diseases. Tight control of LINE‐1 mobilization by the host is crucial for genetic stability. In this study, we report that MOV10 recruits the main decapping enzyme DCP2 to LINE‐1 RNA and forms a complex of MOV10, DCP2, and LINE‐1 RNP, exhibiting liquid–liquid phase separation (LLPS) properties. DCP2 cooperates with MOV10 to decap LINE‐1 RNA, which causes degradation of LINE‐1 RNA and thus reduces LINE‐1 retrotransposition. We here identify DCP2 as one of the key effector proteins determining LINE‐1 replication, and elucidate an LLPS mechanism that facilitates the anti‐LINE‐1 action of MOV10 and DCP2. image LINE‐1 retrotransposition causes genetic instability, increasing the risk of genetic diseases in humans. This study identifies DCP2 as one of the key effectors cooperating with MOV10 to restrict LINE‐1 replication. DCP2 cooperates with MOV10 to decap LINE‐1 mRNA, leading to mRNA decay and impaired LINE‐1 retrotransposition. MOV10 induces the formation of DCP2/MOV10/LINE‐1 complex (DMLC) granules with liquid‐liquid phase separation properties. The DMLC granules play a role in LINE‐1 mRNA decaping by DCP2.