Nayak Prajna, Kejriwal Aarti, Ratnaparkhi Girish S
Indian Institute of Science Education and Research (IISER), Pune, India.
Front Cell Dev Biol. 2021 Sep 30;9:695630. doi: 10.3389/fcell.2021.695630. eCollection 2021.
SUMO conjugation of a substrate protein can modify its activity, localization, interaction or function. A large number of SUMO targets in cells have been identified by Proteomics, but biological roles for SUMO conjugation for most targets remains elusive. The multi-aminoacyl tRNA synthetase complex (MARS) is a sensor and regulator of immune signaling. The proteins of this 1.2 MDa complex are targets of SUMO conjugation, in response to infection. Arginyl tRNA Synthetase (RRS), a member of the sub-complex II of MARS, is one such SUMO conjugation target. The sites for SUMO conjugation are Lys 147 and 383. Replacement of these residues by Arg (RRS ), creates a SUMO conjugation resistant variant (RRS ). Transgenic lines for RRS and RRS were generated by expressing these variants in a animal, using the UAS-Gal4 system. The - line was itself generated using CRISPR/Cas9 genome editing. Expression of both and rescue the lethality. Adult animals expressing and are compared and contrasted for their response to bacterial infection by gram positive and gram negative . We find that , when compared to , shows modulation of the transcriptional response, as measured by quantitative 3' mRNA sequencing. Our study uncovers a possible non-canonical role for SUMOylation of RRS, a member of the MARS complex, in host-defense.
底物蛋白的SUMO化修饰可改变其活性、定位、相互作用或功能。蛋白质组学已鉴定出细胞中大量的SUMO靶标，但大多数靶标的SUMO化修饰的生物学作用仍不清楚。多氨酰tRNA合成酶复合体（MARS）是免疫信号的传感器和调节因子。这个1.2 MDa复合体的蛋白质是SUMO化修饰的靶标，以应对感染。精氨酰tRNA合成酶（RRS）是MARS亚复合体II的成员，就是这样一个SUMO化修饰靶标。SUMO化修饰位点是赖氨酸147和383。用精氨酸（RRS ）取代这些残基，产生了一个抗SUMO化修饰的变体（RRS ）。通过使用UAS-Gal4系统在 动物中表达这些变体，生成了RRS 和RRS 的转基因品系。 品系本身是使用CRISPR/Cas9基因组编辑产生的。 和 的表达都挽救了 的致死性。对表达 和 的成年动物对革兰氏阳性和革兰氏阴性细菌感染的反应进行了比较和对比。我们发现，与 相比， 通过定量3' mRNA测序测量，显示出转录反应的调节。我们的研究揭示了MARS复合体成员RRS的SUMO化修饰在宿主防御中可能具有的非经典作用。
