Northeastern University, Department of Physics, Boston, MA 02115, USA.
The Laboratory of Molecular and Cellular Biology, NIDDK, NIH, Bethesda, MD 20892, USA.
Semin Cell Dev Biol. 2019 Feb;86:140-149. doi: 10.1016/j.semcdb.2018.03.019. Epub 2018 Mar 31.
Long interspersed nuclear element 1 (LINE-1 or L1) is the dominant retrotransposon in mammalian genomes. L1 encodes two proteins ORF1p and ORF2p that are required for retrotransposition. ORF2p functions as the replicase. ORF1p is a coiled coil-mediated trimeric, high affinity RNA binding protein that packages its full- length coding transcript into an ORF2p-containing ribonucleoprotein (RNP) complex, the retrotransposition intermediate. ORF1p also is a nucleic acid chaperone that presumably facilitates the proposed nucleic acid remodeling steps involved in retrotransposition. Although detailed mechanistic understanding of ORF1p function in this process is lacking, recent studies showed that the rate at which ORF1p can form stable nucleic acid-bound oligomers in vitro is positively correlated with formation of an active L1 RNP as assayed in vivo using a cell culture-based retrotransposition assay. This rate was sensitive to minor amino acid changes in the coiled coil domain, which had no effect on nucleic acid chaperone activity. Additional studies linking the complex nucleic acid binding properties to the conformational changes of the protein are needed to understand how ORF1p facilitates retrotransposition.
长散布核元件 1（LINE-1 或 L1）是哺乳动物基因组中主要的反转录转座子。L1 编码两种蛋白质 ORF1p 和 ORF2p，它们是反转录转座所必需的。ORF2p 作为复制酶发挥作用。ORF1p 是一种卷曲螺旋介导的三聚体、高亲和力 RNA 结合蛋白，将其全长编码转录本包装到含有 ORF2p 的核糖核蛋白（RNP）复合物中，即反转录转座中间体。ORF1p 也是一种核酸伴侣，它可能有助于促进反转录转座中涉及的核酸重塑步骤。虽然缺乏对 ORF1p 在该过程中功能的详细机制理解，但最近的研究表明，ORF1p 在体外形成稳定的核酸结合寡聚物的速率与使用基于细胞培养的反转录转座测定法在体内测定的活性 L1 RNP 的形成呈正相关。该速率对卷曲螺旋结构域中的微小氨基酸变化敏感，而这些变化对核酸伴侣活性没有影响。需要进一步研究将复杂的核酸结合特性与蛋白质的构象变化联系起来，以了解 ORF1p 如何促进反转录转座。
