FUS functions in coupling transcription to splicing by mediating an interaction between RNAP II and U1 snRNP

The protein fused-in-sarcoma (FUS) is mutated to cause the neurodegenerative disease amyotrophic lateral sclerosis, but its normal cellular role remains to be understood. Previous work showed that FUS associates with both RNA polymerase II (RNAP II) and the essential splicing factor U1 small nuclear ribonucleoprotein (snRNP). Here we were able to directly investigate the functional significance of these interactions using an in vitro system. We show that FUS is essential for the interaction between U1 snRNP and RNAP II and that FUS must be present during the RNAP II transcription reaction in order for splicing to occur. Together, these data indicate that FUS mediates an interaction between RNAP II and U1 snRNP, thereby physically and functionally coupling transcription to splicing.