AbstractRpb4 and Rpb7, are conserved subunits of RNA polymerase II that play important roles in stress responses such as growth at extreme temperatures, recovery from stationary phase, sporulation and pseudohyphal growth. Recent reports have shown that apart from stress response, these proteins also affect a multitude of processes including activated transcription, mRNA export, transcription coupled repair etc. We propose a model that integrates the multifarious roles of this sub‐complex. We suggest that these proteins function by modulating interactions of one or more ancillary factors with the polymerase leading to specific transcription of subsets of these genes. Preliminary experimental evidence in support of such a model is discussed. IUBMB Life, 57: 93‐102, 2005