Differential contribution of the RNA recognition motifs to SRSF1 protein interaction network
The protein SRSF1, initially identified as a splicing factor, is currently known to participate in a variety of cellular processes. However, its role and regulatory mechanisms in these processes remain incompletely understood. Using a SILAC proteomic approach, we have characterised the SRSF1 interactome, thereby identifying multiple diverse protein interaction partners of SRSF1 and the molecular complexes with which it is associated. Given that the RNA-binding ability of SRSF1 is necessary for many of its activities, we extended the analysis of the SRSF1 interactome to compare the wild type protein against two site-specific SRSF1 variants, bearing mutations in each of its two RNA recognition motifs (RRMs). The first mutation disrupted the canonical RRM (RRM1), while the second affected the pseudo-RRM (RRM2). Interestingly, the data show clear differences between the SRSF1 interacting proteins, depending on the functional status of each RRM domain. In particular, a functional RRM1 was critical for maintaining interactions with multiple partners, especially those involved in translation-related processes, showing a far greater loss of interactions upon mutation than RRM2. This study provides valuable new insights into the broader cellular roles and interaction landscape of SRSF1.