The 12-subunit RNA polymerase II enzyme in yeasts and higher eukaryotic cells is important for transcription of protein-coding genes. Its fourth and seventh largest subunits named Rpb4 and Rpb7, respectively, display some unique features that distinguish them from the remaining subunits of this enzyme. These two subunits also bind to each other forming a complex in archaebacteria, yeasts, plants and humans. Our knowledge about the structure and functions of this complex has greatly advanced in recent years. These subunits were initially considered to be important only for initiation of transcription and stress response. However, recent evidence suggests that they are not only involved in transcription, but also in DNA repair, mRNA export and decay as well as translation, highlighting the roles of this heterodimer in diverse biological processes. In this article, we review the current status of these two subunits and discuss attributes of their structure and function across organisms.