The Codependent Expression of Yeast RNA Polymerase I Rpa34/Rpa49 Heterodimer Subcomplex

Abstract

Dysregulation of RNA polymerase I (Pol I) is a hallmark of many cancers and several developmental disorders. Pol I is a multi‐subunit complex that synthesizes ribosomal RNA (rRNA), the integral structural and catalytic component of the ribosome. A key yeast Pol I subcomplex that functions in nearly every step of the transcription cycle is the Rpa34/Rpa49 heterodimer. Recent studies with the heterodimer's human counterpart have shown species specific differences in terms of the heterodimer’s importance for cell growth and functional domain requirements. To further explore these differences, we used the yeast model system to show that similarly to humans, the yeast heterodimer subunits exhibit codependent expression. We further analyzed this codependence in terms of specific heterodimer domain requirements and the level of gene expression the codependence occurs. We found that Rpa34/Rpa49 codependence occurs at the post translational level in a manner dependent on Rpa49’s dimerization domain. Overall, our findings suggest that the codependent expression of yeast and human Rpa34/Rpa49 subcomplexes is an evolutionarily conserved feature that may apply to other Pol I, II, and III subcomplexes.