Flexibility of the jaw-lobe region in RNA polymerase I influences transcriptional elongation

Abstract

In growing eukaryotic cells, most transcriptional activity involves synthesis of ribosomal RNA (rRNA) by RNA polymerase I (Pol I). Yeast Pol I is composed by 14 subunits with an overall mass of 600 kDa. Deletion of Pol I subunit A49, which plays a role both in transcription initiation and elongation, causes a severe growth defect. Genetic analysis allowed us to isolate a set of mutants on different Pol I subunits that suppress the A49 deletion phenotype. Most suppressor mutants cluster at the Pol I jaw-lobe region, which encompasses the jaw in subunit A190, the lobe in subunit A135, and the N-terminal and liker domains of subunit A12. We use computational analysis of available Pol I structures to propose a role for the jaw-lobe region in the transition between transcription initiation and elongation. Finally, we show that the most efficient suppressor mutant exhibits increased rRNA production both in vivo and in vitro.