Paraspeckles: paragons of functional aggregation

Abstract

Low-complexity proteins undergo phase separation in vitro, forming hydrogels or liquid droplets. Whether these form in vivo, and under what conditions, is still unclear. In this issue, Hennig et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201504117) show that formation of the paraspeckle, a nuclear body that regulates gene expression, requires low-complexity prion-like domains (PLDs) within paraspeckle proteins. The same proteins were shown to form hydrogels, shedding light on the role of "functional aggregation" in nuclear substructure.

Figure 1.

Low-complexity proteins and the formation of cellular bodies in health and disease. In normal body function (top), low-complexity proteins coordinate the sequestration of precursor molecules, which can be either RNA or proteins. Within the body, these components are assembled into functional complexes, which then leave the body for a function, such as product generation (green). In disease (bottom), low-complexity proteins can form aggregates that are toxic and may prevent bodies from functioning normally. This results in a depletion of functional complexes and the release of precursor into the nucleoplasm and/or cytoplasm.