Investigating the microphase architecture of nuclear speckles

This study posits that specific proteins drive the internal organisation of nuclear speckles through mechanisms resembling block copolymer chemistry. It represents a biophysical characterisation, seemingly conducted to isolate molecular behaviours from the noise of a living cell. The central claim is that the interplay of folded domains and disordered regions in proteins dictates the formation of size-limited assemblies.

The investigation focused on serine/arginine-rich splicing factors (SRSFs) and TDP-43. These components contain both folded RNA recognition motifs and disordered regions. The data indicates these proteins possess specific patterns of attraction and repulsion. Consequently, they do not merely aggregate. They undergo 'microphase separation'. This process yields ordered assemblies rather than chaotic clumps.

Microphases within nuclear speckles

Measurements place these microphases between 23 and 45 nanometres in diameter. Each unit comprises roughly tens of molecules. When observed at a sub-micron scale, the cellular assemblies appear consistent with clusters of these smaller units. Furthermore, the introduction of the long non-coding RNA MALAT1 altered the stability of these formations. Specifically, MALAT1 appeared to bind preferentially to SRSF1 while destabilising TDP-43. This suggests a regulatory function.

In protein mixtures, the interaction between these microphases resulted in micron-scale structures. These exhibited a 'core-shell' organisation, described by the authors as double-emulsion structures. While the physical principles of copolymer interactions are well-established in materials science, applying them to cellular biology requires caution. The study demonstrates how these interactions occur in isolation. Whether this precise 'core-shell' geometry holds true in the dynamic, crowded environment of a functioning nucleus remains a question for in vivo validation.