Controlled by disorder: Phosphorylation modulates SRSF1 domain availability for spliceosome assembly.

ABSTRACT: Serine/arginine-rich splicing factor 1 (SRSF1) is key in the mRNA lifecycle including transcription, splicing, nonsense-mediated decay, and nuclear export. Consequently, its dysfunction is linked to cancers, viral evasion, and developmental disorders. The functionality of SRSF1 relies on its interactions with other proteins and RNA molecules. These processes are regulated by phosphorylation of its unstructured arginine/serine-rich tail (RS). Here, we characterize how phosphorylation affects SRSF1's protein and RNA interaction and phase separation. Using NMR paramagnetic relaxation enhancement and chemical shift perturbation, we find that when unphosphorylated, SRSF1's RS interacts with its first RNA-recognition motif (RRM1). Phosphorylation of RS decreases its interactions with the protein

SUBMITTER: Fargason T 

PROVIDER: S-EPMC11836896 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature