Structural basis for RNA polymerase III transcription repression by Maf1

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Maf1 is a crucial regulator of RNA polymerase III (Pol III).
• Pol III controls the transcription of essential non-coding RNAs.
• Maf1's role in regulating cellular processes like metabolism and lifespan is known, but its precise mechanism of inhibition is unclear.

Purpose of the Study:

• To elucidate the structural mechanism by which Maf1 inhibits RNA polymerase III (Pol III).
• To provide a high-resolution structure of the Maf1-Pol III complex.

Main Methods:

• Cryo-electron microscopy (cryo-EM) at 3.3-Å resolution.
• Structural analysis of yeast Maf1 bound to Pol III.

Main Results:

• The cryo-EM structure reveals how Maf1 binds to Pol III.
• Maf1 sequesters key Pol III elements essential for transcription initiation.
• Maf1 binds the mobile C34 winged helix 2 domain, effectively sealing the active site.
• The Maf1 binding site significantly overlaps with the binding site of TFIIIB, a transcription initiation factor.

Conclusions:

• Maf1 inhibits Pol III transcription by physically blocking the active site and interfering with initiation factor binding.
• This structural insight clarifies Maf1's role as a conserved inhibitor of Pol III.
• Understanding Maf1-Pol III interaction may offer new avenues for targeting Pol III-dependent processes.