Long Interspersed Nuclear Element-1 (LINE-1 or L1) is a retrotransposable element that autonomously replicates in the human genome, resulting in DNA damage and genomic instability. Activation of L1 in senescent cells triggers a type I interferon response and age-associated inflammation. Two open reading frames encode an ORF1 protein functioning as mRNA chaperone and an ORF2 protein providing catalytic activities necessary for retrotransposition. No function has been identified for the conserved, disordered N-terminal region of ORF1. Using microscopy and NMR spectroscopy, we demonstrate that ORF1 forms liquid droplets in vitro in a salt-dependent manner and that interactions between its N-terminal region and coiled-coil domain are necessary for phase separation. Mutations disrupting blocks of charged residues within the N-terminus impair phase separation while some mutations within the coiled-coil domain enhance phase separation. Demixing of the L1 particle from the cytosol may provide a mechanism to protect the L1 transcript from degradation.

中文翻译：

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LINE-1 ORF1蛋白的相分离由N末端和卷曲螺旋结构域介导

长散布的核元件-1（LINE-1或L1）是可逆转座的元件，可在人类基因组中自主复制，从而导致DNA损伤和基因组不稳定。L1在衰老细胞中的激活会触发I型干扰素反应和与年龄相关的炎症。两个开放阅读框编码充当mRNA分子伴侣的ORF1蛋白和提供逆转座所需催化活性的ORF2蛋白。对于ORF1的保守的，无序的N末端区域，尚未鉴定出功能。使用显微镜和NMR光谱，我们证明ORF1以盐依赖性方式在体外形成液滴，并且其N末端区域和卷曲螺旋结构域之间的相互作用对于相分离是必需的。突变破坏N端内带电残基的嵌段会损害相分离，而卷曲螺旋结构域内的某些突变会增强相分离。L1颗粒与细胞质的分离可以提供一种保护L1转录本不受降解的机制。