SON and SRRM2 are essential for nuclear speckle formation

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Nuclear speckles (NS) are prominent biomolecular condensates, but their organizing core remains unidentified.
• Current research on NS function is limited, primarily relying on colocalization studies.
• The SC35 antibody, commonly used to mark NS, was found to target SRRM2, not previously recognized.

Purpose of the Study:

• To identify the essential components forming the organizing core of nuclear speckles.
• To investigate the roles of SON and SRRM2 in nuclear speckle assembly and stability.
• To establish a foundation for studying nuclear speckle functions in physiological and stress contexts.

Main Methods:

• Utilized a monoclonal antibody (SC35) and identified its primary target as SRRM2.
• Performed depletion studies of SON and SRRM2 proteins.
• Investigated the effect of SRRM2 intrinsically disordered regions (IDRs) deletion on NS structure.

Main Results:

• Established that SRRM2 is the main target of the SC35 antibody.
• Demonstrated that SON depletion causes partial NS disassembly.
• Showed that co-depletion of SON and SRRM2, or SON depletion in SRRM2 IDR-deleted cells, leads to near-complete NS dissolution.

Conclusions:

• SON and SRRM2 are identified as the likely core components responsible for nuclear speckle formation.
• The study corrects the characterization of the SC35 antibody, highlighting SRRM2's role.
• This work provides a critical basis for future investigations into nuclear speckle functions.