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- W4367297977 abstract "LINE-1 (L1) is the only autonomously active retrotransposon in the human genome, and accounts for 17% of the human genome. The L1 mRNA encodes two proteins, ORF1p and ORF2p, both essential for retrotransposition. ORF2p has reverse transcriptase and endonuclease activities, while ORF1p is a homotrimeric RNA-binding protein with poorly understood function. Here, we show that condensation of ORF1p is critical for L1 retrotransposition. Using a combination of biochemical reconstitution and live-cell imaging, we demonstrate that electrostatic interactions and trimer conformational dynamics together tune the properties of ORF1p assemblies to allow for efficient L1 ribonucleoprotein (RNP) complex formation in cells. Furthermore, we relate the dynamics of ORF1p assembly and RNP condensate material properties to the ability to complete the entire retrotransposon life-cycle. Mutations that prevented ORF1p condensation led to loss of retrotransposition activity, while orthogonal restoration of coiled-coil conformational flexibility rescued both condensation and retrotransposition. Based on these observations, we propose that dynamic ORF1p oligomerization on L1 RNA drives the formation of an L1 RNP condensate that is essential for retrotransposition." @default.
- W4367297977 created "2023-04-29" @default.
- W4367297977 creator A5000835898 @default.
- W4367297977 creator A5025650361 @default.
- W4367297977 creator A5037810069 @default.
- W4367297977 creator A5075536007 @default.
- W4367297977 creator A5079485481 @default.
- W4367297977 creator A5081521084 @default.
- W4367297977 date "2023-04-28" @default.
- W4367297977 modified "2023-10-01" @default.
- W4367297977 title "Condensation of LINE-1 is critical for retrotransposition" @default.
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