NS1 binding protein regulates stress granule dynamics and clearance by inhibiting p62 ubiquitination.

Jeon, Pureum; Ham, Hyun-Ji; Choi, Haneul; Park, Semin; Jang, Jae-Woo; Park, Sang-Won; Cho, Dong-Hyung; Lee, Hyun-Jeong; Song, Hyun Kyu; Komatsu, Masaaki; Han, Dohyun; Jang, Deok-Jin; Lee, Jin-A

The NS1 binding protein, known for interacting with the influenza A virus protein, is involved in RNA processing, cancer, and nerve cell growth regulation. However, its role in stress response independent of viral infections remains unclear. This study investigates NS1 binding protein's function in regulating stress granules during oxidative stress through interactions with GABARAP subfamily proteins. We find that NS1 binding protein localizes to stress granules, interacting with core components, GABARAP proteins, and p62, a protein involved in autophagy. In cells lacking NS1 binding protein, stress granule dynamics are altered, and p62 ubiquitination is increased, suggesting impaired stress granule degradation. Overexpression of NS1 binding protein reduces p62 ubiquitination. In amyotrophic lateral sclerosis patient-derived neurons, reduced NS1 binding protein and p62 disrupt stress granule morphology. These findings identify NS1 binding protein as a negative regulator of p62 ubiquitination and a facilitator of GABARAP recruitment to stress granules, implicating it in stress granule regulation and amyotrophic lateral sclerosis pathogenesis. The NS1 binding protein (NS1-BP) is involved in RNA processing, cancer, and nerve cell growth regulation. Here, the authors show that NS1-BP regulates stress granule (SG) dynamics under oxidative stress by interacting with GABARAPs and p62. Reduced NS1-BP in amyotrophic lateral sclerosis (ALS) neurons affects SG morphology, linking it to ALS.

STRESS granules; CYTOLOGY; AMYOTROPHIC lateral sclerosis; CARRIER proteins; LIFE sciences

Nature Communications, 2024, Vol 15, Issue 1, p1

2041-1723

Academic Journal

10.1038/s41467-024-55446-w