Seminar

Crystal structure of RNA polymerase I

CARLOS FERNÁNDEZ TORNERO, PhD

Biosynthesis of the eukaryotic ribosome starts with ribosomal RNA production by RNA polymerase I (Pol I), a process that is critical to regulate cell growth and proliferation. We were able to obtain the crystal structure of yeast Pol I, a 14-subunit complex composed of more than 80,000 atoms with a total mass of 590 kDa, at 3.0 Å resolution [1, 2]. The structure represents the latent state of the enzyme, characterized by three major features. First, it forms dimers that involve the C-terminal tail of the stalk subunit A43. Second, the two enzyme halves pivot along the DNA-binding cleft to produce an open cleft and an unfolded bridge helix. Third, an extended loop in subunit A190 mimics the DNA backbone along the cleft, hampering nucleic acid binding. The Pol I crystal structure also reveals intrinsic modules that only bind transiently in other RNA polymerases, such as a TFIIS-like zinc ribbon in subunit A12.2 and a TFIIF-like dimerization module in the A49/A34.5 heterodimer.