Eukaryotic cells contain a number of large assemblies consisting of RNA and protein collectively referred to as RNP granules. RNP granules are found in the nucleus (e.g. Cajal bodies, Paraspeckles and the Nucleolus) and the cytosol (e.g. P-bodies and Stress granules). RNP granules are involved in diverse roles including RNA localization, the control of translation and mRNA decay, modulating the stress response, as well as the transport and control of localized mRNAs in neurons and embryos. Analysis of stress granules from yeast and mammalian cells identified a diverse proteome within stress granules including many ATP-dependent remodeling complexes. Genetic experiments demonstrate that numerous remodeling complexes affect both the assembly and disassembly of eukaryotic stress granules. Such remodeling complexes may also play a role in the assembly and disassembly of RNA-protein aggregates that form in some human diseases. Stress granules, and likely other RNP granules, form in part through intermolecular RNA-RNA interactions, although the process of RNA self-assembly and its regulation in cells is not understood. In vitro, we demonstrate that the minimization of surface free energy leads to sequence dependent patterning of RNA self-assembly, as well as the recruitment of RNAs to the surfaces of RNA or RNP assemblies. In addition, the ATPase activity of the abundant DEAD-box helicase eIF4A limits RNA self-assembly in vitro, and reduces RNA recruitment to stress granules in cells, thereby limiting stress granule assembly. This defines a new role for eIF4A, and other RNA helicases, to limit non-specific intermolecular RNA-RNA interactions in cells, allowing for proper RNP function.

RNP granules in health and disease

2019 Fall National Meeting

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