Nature Communications ( IF 14.7 ) Pub Date : 2022-11-03 , DOI: 10.1038/s41467-022-34225-5 Emily L Spaulding 1 , Alexis M Feidler 1 , Lio A Cook 1 , Dustin L Updike 1
The intrinsically disordered RG/RGG repeat domain is found in several nucleolar and P-granule proteins, but how it influences their phase separation into biomolecular condensates is unclear. We survey all RG/RGG repeats in C. elegans and uncover nucleolar and P-granule-specific RG/RGG motifs. An uncharacterized protein, K07H8.10, contains the longest nucleolar-like RG/RGG domain in C. elegans. Domain and sequence similarity, as well as nucleolar localization, reveals K07H8.10 (NUCL-1) to be the homolog of Nucleolin, a protein conserved across animals, plants, and fungi, but previously thought to be absent in nematodes. Deleting the RG/RGG repeats within endogenous NUCL-1 and a second nucleolar protein, GARR-1 (GAR1), demonstrates these domains are dispensable for nucleolar accumulation. Instead, their RG/RGG repeats contribute to the phase separation of proteins into nucleolar sub-compartments. Despite this common RG/RGG repeat function, only removal of the GARR-1 RG/RGG domain affects worm fertility and development, decoupling precise sub-nucleolar structure from nucleolar function.
中文翻译:
核仁蛋白和 GAR1 的线虫同源物中的 RG/RGG 重复有助于亚核仁相分离
在几种核仁和 P 颗粒蛋白中发现了本质上无序的 RG/RGG 重复结构域,但它如何影响它们形成生物分子凝聚物的相分离尚不清楚。我们调查了秀丽隐杆线虫中的所有 RG/RGG 重复序列,并发现了核仁和 P 颗粒特异性 RG/RGG 基序。一种未表征的蛋白质 K07H8.10 包含秀丽隐杆线虫中最长的核仁样 RG/RGG 结构域。结构域和序列相似性以及核仁定位表明 K07H8.10 (NUCL-1) 是 Nucleolin 的同源物,Nucleolin 是一种在动物、植物和真菌中保守的蛋白质,但之前认为在线虫中不存在。删除内源性 NUCL-1 和第二种核仁蛋白 GARR-1 (GAR1) 内的 RG/RGG 重复序列表明这些结构域对于核仁积累是可有可无的。相反,它们的 RG/RGG 重复序列有助于蛋白质相分离到核仁亚区室中。尽管有这种常见的 RG/RGG 重复功能,但只有去除 GARR-1 RG/RGG 结构域才会影响线虫的生育力和发育,从而将精确的亚核仁结构与核仁功能分离。