RNA Pol II preferentially regulates ribosomal protein expression by trapping disassociated subunits

Abstract

RNA polymerase II (RNA Pol II) has been recognized as a passively regulated multi-subunit holoenzyme. However, the extent to which RNA Pol II subunits might be important beyond the RNA Pol II complex remains unclear. Here, fractions containing disassociated RPB3 (dRPB3) were identified by size exclusion chroma-tography in various cells. Through a unique strategy, i.e., "specific degradation of disassociated subunits (SDDS),"we demonstrated that dRPB3 functions as a regulatory component of RNA Pol II to enable the preferential control of 30 end processing of ribosomal protein genes directly through its N-terminal domain. Machine learning analysis of large-scale genomic features revealed that the little elongation complex (LEC) helps to specialize the functions of dRPB3. Mechanistically, dRPB3 facilitates CBC-PCF11 axis activity to in-crease the efficiency of 30 end processing. Furthermore, RPB3 is dynamically regulated during development and diseases. These findings suggest that RNA Pol II gains specific regulatory functions by trapping disas-sociated subunits in mammalian cells.