Elucidating the mechanisms underlying mRNA translation regulation by condensation (B1)

The goal of of B1 is to characterize the molecular interaction landscape of immobile and mobile (translationally silenced and competent) nature of RNA molecules inside RNP granules to provide a mechanistic under-standing of regulation in condensates and disease phenotypes

RNP granules, such as neuronal transport granules (NTGs) or stress-induced RNP granules (SGs), are condensates that play key roles in translation regulation. Their aberrant state is as-sociated with neurodegeneration and cancer. RNP granule assembly and the underlying regula-tory mechanisms are not understood. Our preliminary data show that the RNA-binding protein Ras GTPase-activating protein-binding protein 1 (G3BP1) interacts with unfolded RNA molecules to assemble RNP granules. RNA accumulation in granules leads to RNA-RNA interactions, inhibiting RNA mobility and translatability. The DEAD-box RNA helicase (DDX3X) localizes to RNP granules to attenuate RNA-RNA interactions, rendering the condensates dynamic and ena-bling mRNA translation. DDX3X disease variants cannot resolve RNA-RNA interactions causing RNA granule persistence. We suggest that RNP granules mediate inhibitory RNA-RNA interactions, which must be modulated by RNA helicases to regulate RNA availability and translatability.

1. How do RNP granules regulate RNA availability and translatability in physiology and disease?
2. How do RNA helicases regulate RNA structure, dynamics, and organization within RNP granules?

Topic 1: RNA structures and dynamics in multi-component biomolecular condensates (Schlierf)
Topic 2: Revealing the functional role of RNA-protein condensates in regulating RNA availability (Alberti)

The PhD students will be trained in smFRET and FCS and analysis, advanced imaging and analysis, protein biochemistry and RNP-like granule reconstitution.

• Candidates have a Masters degree in physics, biology or related fields
• Candidates should have a sound basis in biochemistry, biophysics, enzymology, quantitative biology, or closely related fields.
• Experience in microscopy, in vitro reconstitution, and protein isolation methods are expected

We are currently recruiting the first cohort of motivated doctoral candidates to join our research training group “RTG 3120 Biomolecular Condensates”. If you are a potential applicant, register and complete the following form . If you have questions about the research topic, then email the project supervisor >