Luca Chiara De, Gupta Anuj, Bortvin Alex
bioRxiv. 2023 Jan 13:2023.01.09.523313. doi: 10.1101/2023.01.09.523313.
Transposable elements (TE) are mobile DNA sequences whose excessive proliferation endangers the host. Although animals have evolved robust TE-targeting defenses, including Piwi-interacting (pi)RNAs, retrotransposon LINE-1 (L1) still thrives in humans and mice. To gain insights into L1 endurance, we characterized L1 Bodies (LBs) and ORF1p complexes in germ cells of piRNA-deficient null mice. We report that ORF1p interacts with TE RNAs, genic mRNAs, and stress granule proteins, consistent with earlier studies. We also show that ORF1p associates with the CCR4-NOT deadenylation complex and PRKRA, a Protein Kinase R factor. Despite ORF1p interactions with these negative regulators of RNA expression, the stability and translation of LB-localized mRNAs remain unchanged. To scrutinize these findings, we studied the effects of PRKRA on L1 in cultured cells and showed that it elevates ORF1p levels and L1 retrotransposition. These results suggest that ORF1p-driven condensates promote L1 propagation, without affecting the metabolism of endogenous RNAs.
转座元件（TE）是可移动的DNA序列，其过度增殖会危及宿主。尽管动物已经进化出强大的靶向TE的防御机制，包括与Piwi相互作用的（pi）RNA，但逆转座子LINE-1（L1）在人类和小鼠中仍然活跃。为了深入了解L1的耐受性，我们对piRNA缺陷型小鼠生殖细胞中的L1小体（LBs）和ORF1p复合物进行了表征。我们报告称，ORF1p与TE RNA、基因mRNA和应激颗粒蛋白相互作用，这与早期研究一致。我们还表明，ORF1p与CCR4-NOT去腺苷酸化复合物和PRKRA（一种蛋白激酶R因子）相关联。尽管ORF1p与这些RNA表达的负调节因子相互作用，但LB定位的mRNA的稳定性和翻译保持不变。为了仔细研究这些发现，我们在培养细胞中研究了PRKRA对L1的影响，结果表明它提高了ORF1p水平和L1逆转座。这些结果表明，ORF1p驱动的凝聚物促进L1传播，而不影响内源性RNA的代谢。
