Hypo- and Hyper-Assembly Diseases of RNA–Protein Complexes

A key aspect of cellular function is the proper assembly and utilization of ribonucleoproteins (RNPs). Recent studies have shown that hyper- or hypo-assembly of various RNPs can lead to human diseases. Defects in the formation of RNPs lead to ‘RNP hypo-assembly diseases’, which can be caused by RNA degradation outcompeting RNP assembly. By contrast, excess RNP assembly, either in higher order RNP granules, or due to the expression of repeat-containing RNAs, can lead to ‘RNP hyper-assembly diseases’. Here, we discuss the most recent advances in understanding the cause of disease onset, as well as potential therapies from the aspect of modulating RNP assembly in the cell, which presents a novel route to the treatment of these diseases.

TrendsMutations in RNP assembly components can lead to RNP hypo-assembly diseases by triggering RNA decay.Prevention of RNA decay could be a viable therapeutic strategy for RNP hypo-assembly diseases.Mutation in RNA binding proteins lead to RNP hyper-assembly and formation of persistent stress granules.Persistence of stress granules due to loss of disassembly pathways could also lead to the same family of RNP hyper-assembly diseases.Repeat expansions in RNAs could lead to toxicity through multiple potential mechanisms.Therapeutic strategies for RNP hyper-assembly diseases include prevention of stress granule persistence and modulation of cellular signaling pathways, as well as targeted disruption of constituent RNA–protein interactions.