Liquid-liquid phase separation: Galectin-3 in nuclear speckles and ribonucleoprotein complexes

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Nuclear speckles are key nuclear bodies involved in RNA splicing.
• These structures, including those marked by SC35, are now understood as liquid phase condensates.
• Galectin-3 has been observed to co-localize with SC35 in nuclear speckles.

Purpose of the Study:

• To review the key features of galectin-3 that enable its localization within liquid phase condensates.
• To highlight the role of intrinsically disordered domains, oligomerization, and RNA association in galectin-3's phase separation behavior.

Main Methods:

• Review of existing literature on nuclear speckles, galectin-3, and liquid phase separation.
• Analysis of studies demonstrating galectin-3's molecular properties relevant to phase condensation.
• Immunofluorescence and co-localization studies of galectin-3 and SC35.

Main Results:

• Galectin-3 exhibits three critical features for liquid condensate localization: an intrinsically disordered domain, propensity for oligomer formation enabling multivalent interactions, and association with RNA and ribonucleoprotein complexes.
• These properties facilitate galectin-3's incorporation into phase-separated nuclear speckles.
• The co-localization of galectin-3 with SC35 in nuclear speckles confirms its presence in these endogenous cellular condensates.

Conclusions:

• Galectin-3's localization in nuclear speckles is driven by its biophysical properties consistent with participation in liquid phase separation.
• Understanding these features provides insight into the dynamic organization of nuclear speckles and the role of galectin-3 within them.
• This review consolidates evidence for galectin-3 as a component of functional, phase-separated nuclear bodies.