AI Article Synopsis
- Stress granules form when RNA binding proteins and RNA come together during stress, with certain mutations increasing the likelihood of amyloid fibril formation.
- The interactions between the low complexity domains (PLCDs) in proteins can be categorized into those that encourage condensate formation and those that lead to more stable fibril formation, allowing for different behaviors in stress granules.
- By enhancing the stability of these condensates through specific mutations, researchers were able to counteract the effects of ALS-associated mutations, suggesting a potential strategy for suppressing harmful fibril formation by improving condensate stability.
Article Abstract
Stress granules form via co-condensation of RNA binding proteins with prion-like low complexity domains (PLCDs) and RNA molecules released by stress-induced polysomal runoff. Homotypic interactions among PLCDs can drive amyloid fibril formation and this is enhanced by ALS-associated mutations. We find that homotypic interactions that drive condensation versus fibril formation are separable for A1-LCD, the PLCD of hnRNPA1. These separable interactions lead to condensates that are metastable versus fibrils that are globally stable. Metastable condensates suppress fibril formation, and ALS-associated mutations enhance fibril formation by weakening condensate metastability. Mutations designed to enhance A1-LCD condensate metastability restore wild-type behaviors of stress granules in cells even when ALS-associated mutations are present. This suggests that fibril formation can be suppressed by enhancing condensate metastability through condensate-driving interactions.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925303 | PMC |
| http://dx.doi.org/10.1101/2024.02.28.582569 | DOI Listing |
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