Molecular Structures of Transcribing RNA Polymerase I

Area of Science:

• Structural biology
• Molecular biology
• Biochemistry

Background:

• RNA polymerase I (Pol I) is a large, multi-subunit enzyme responsible for synthesizing pre-ribosomal RNA.
• Understanding Pol I structure and function is critical for regulating ribosome biogenesis.

Purpose of the Study:

• To elucidate the structural mechanisms of RNA polymerase I elongation complex formation.
• To provide atomic-level insights into the Pol I transcription cycle.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine high-resolution structures.
• Structures were obtained for elongating Pol I and a Pol I open complex.

Main Results:

• Three cryo-EM structures of elongating Pol I (4.0 Å and 4.6 Å) and one open complex (3.8 Å) were determined.
• Two modules in Pol I were identified that narrow the DNA-binding cleft via clamp domain closure.
• Conformational changes, including bridge helix folding and A12.2 C-terminal domain displacement, were observed during elongation complex formation.

Conclusions:

• The study reveals key conformational changes during Pol I elongation complex assembly.
• These structures offer unprecedented insight into the molecular architecture and transcription cycle of RNA polymerase I.