The gene-regulating proteins NONO and SFPQ assemble into ordered filaments

Area of Science:

• Molecular Biology
• Structural Biology
• Gene Regulation

Background:

• Proteins of the Drosophila behaviour/human splicing (DBHS) family are vital for gene regulation, including transcription, splicing, and DNA repair.
• DBHS proteins form dimers and higher-order oligomers via globular domains and α-helical coiled-coils, essential for their functions.
• The precise arrangement of DBHS proteins in higher oligomers remained structurally undetermined.

Purpose of the Study:

• To elucidate the atomic structure of filamentous NONO/SFPQ heterooligomers.
• To understand the molecular mechanisms underlying the formation and stabilization of these higher-order protein structures.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to resolve the structure of the NONO/SFPQ heterooligomer.
• Structural analysis focused on identifying the interactions stabilizing the filamentous assembly.

Main Results:

• The study presents the first atomic structure of a filamentous NONO/SFPQ heterooligomer.
• The resolved filaments adopt a double-helical conformation.
• This double helix is stabilized by an intricate, interdigitating network of coiled-coil interactions between NONO and SFPQ proteins.

Conclusions:

• The determined double-helical structure provides novel insights into the higher-order organization of DBHS family proteins.
• This structural understanding is critical for comprehending the diverse roles of NONO/SFPQ in gene regulation and maintenance.
• The findings lay the groundwork for future investigations into the functional implications of these filamentous assemblies.