The SRI domain is a small three-helix domain originally discovered near the C-terminus of both histonemethyltransferase SETD2 and helicase RECQL5. The SRI domain binds to the C-terminal repeatdomain of the largest subunit of RNA polymerase II, allowing SETD2 and RECQL5 to regulate variousmechanisms associated with RNA transcription. Using original tools to detect common patterns indistantly related sequences, we have identified SRI domains in several additional proteins, mostof which are involved in RNA metabolism. Combining sequence analysis with structural prediction,we show that this domain family is more diverse than previously thought and we predict criticalstructural and functional features.