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Researchers reveal the critical role of RNA in modulating the autolysis of protein adsorbates


Hairpin loop of pre-mRNA. Highlight the nucleolar bases (green) and the ribose-phosphate backbone (blue). Note that this is a single strand of RNA that folds back on itself. Credit: Fossman/Wikipedia

A research group led by Professor Zhang Hong of the Institute of Biophysics of the Chinese Academy of Sciences has shown that RNA acts as a switch to alter the fate of protein condensers dissociated from stages from self-degradation to stress-induced accumulation. The study has been published online in Journal of Cell Biology.

Autophagy is a lysosome-mediated degradation process. Protein condensates assembled via liquid-liquid phase separation (LLPS) can be effectively degraded by autophagy. However, it can avoid self-deterioration under stress or pathological conditions to confer stress resistance or contribute to the pathogenesis of various diseases.

For example, previous studies from Professor Zhang’s lab found that oocyte-derived PGL proteins (PGL-1 and PGL-3) are removed by autophagy in somatic cells during C. elegans embryonic development under normal developmental conditions (15). -25 degrees Celsius). Degradation of PGL-1/-3 requires the receptor protein SEPA-1 and the scaffold protein EPG-2. However, in embryos placed under heat stress conditions, PGL proteins escape self-degradation, and accumulate in a large number of granules to confer stress resistance.

In this study, the researchers found that PGL granules formed under conditions of heat stress contain proteins involved in mRNA metabolism such as the eIF4E homolog IFE-1. RNA-FISH assays revealed that RNA is also sorted into PGL granules in heat-stressed embryos.

Next, the authors found that sorting mRNA into PGL granules regulates autophagic degradation, and that depleting factors involved in mRNA processing, transport, and translation reduce mRNA recruitment to PGL granules and enhance their autophagic degradation, whereas mRNA degradation increases recruitment. of mRNA into PGL granules and promotes their accumulation.

PGL-1/-3/SEPA-1 proteins undergo LLPS to aggregate into PGL repressors. EPG-2 promotes the liquid-to-gel-like transition of PGL suppressors, which is required for autophagosome degradation. The authors showed that mRNA enhances LLPS and maintains fluidity of PGL repressors, as well as inhibiting EPG-2 recruitment. They also found that factors affecting the recruitment of mRNAs to PGL granules modulate the co-localization of EPG-2 and PGL granules in heat-stressed fetuses. These results indicate that mRNAs modulate the autolysis of PGL granules by inhibiting the recruitment of the gel-promoting scaffolding protein EPG-2.

This study reveals the critical role of RNA in shifting the fate of phase-dissociated protein condensers from self-degradation to stress-induced accumulation, providing new insights into the accumulation of nucleoprotein aggregates associated with the pathogenesis of various diseases.

more information:
Hui Zheng et al, RNA recruitment switches the fate of protein suppressors from self-degradation to accumulation, Journal of Cell Biology (2023). doi: 10.1083/jcb.202210104

Provided by the Chinese Academy of Sciences

the quote: Researchers reveal the critical role of RNA in modulating the autolysis of protein repressors (2023, April 6), Retrieved April 6, 2023 from https://phys.org/news/2023-04-reveal-crucial-role-rna -modulation. html

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