The CCHCR1-UBAP2L Interaction Promotes UBAP2L Release from P-Bodies for Stress Granule Assembly.

Ribonucleoprotein granules such as processing bodies (P-bodies) and stress granules (SGs) are membrane-less organelles that regulate mRNA metabolism through liquid-liquid phase separation. UBAP2L drives SG assembly and can bridge P-bodies with SGs, yet how it is mobilized between these compartments remains unclear. Here, using co-immunoprecipitation, GST pull-down, CRISPR-Cas9-mediated knockout, and immunofluorescence microscopy, we demonstrate that CCHCR1 directly binds UBAP2L and that this interaction is dynamically regulated by stress intensity. Under mild oxidative stress, CCHCR1 retains UBAP2L in P-bodies; as stress intensifies, this interaction weakens, permitting UBAP2L release for SG assembly. CCHCR1 deficiency aberrantly traps UBAP2L in P-bodies via enhanced DDX6 association, resulting in defective SG assembly, delayed maturation, and increased P-body-SG fusion. These findings establish CCHCR1 as a stress-responsive switch that controls UBAP2L partitioning between P-bodies and stress granules, thereby controlling the threshold and kinetics of SG biogenesis.