The promiscuity of the SAGA complex subunits: Multifunctional or moonlighting proteins?

Gene expression, the decoding of DNA information into accessible instructions for protein synthesis, is a complex process in which multiple steps, including transcription, mRNA processing and mRNA export, are regulated by different factors. One of the first steps in this process involves chemical and structural changes in chromatin to allow transcription. For such changes to occur, histone tail and DNA epigenetic modifications foster the binding of transcription factors to promoter regions. The SAGA coactivator complex plays a crucial role in this process by mediating histone acetylation through Gcn5, and histone deubiquitination through Ubp8 enzymes. However, most SAGA subunits interact physically with other proteins beyond the SAGA complex. These interactions could represent SAGA-independent functions or a mechanism to widen SAGA multifunctionality. Among the different mechanisms to perform more than one function, protein moonlighting defines unrelated molecular activities for the same polypeptide sequence. Unlike pleiotropy, where a single gene can affect different phenotypes, moonlighting necessarily involves separate functions of a protein at the molecular level. In this review we describe in detail some of the alternative physical interactions of several SAGA subunits. In some cases, the alternative role constitutes a clear moonlighting function, whereas in most of them the lack of molecular evidence means that we can only define these interactions as promiscuous that require further work to verify if these are moonlighting functions.