Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer

Abstract

Serine/Arginine Splicing Factor 1 (SRSF1) is the archetype member of the SR protein family of splicing regulators. Since its discovery over two decades ago, SRSF1 has been repeatedly surprising and intriguing investigators by the plethora of complex biologic pathways it regulates. These include several key aspects of mRNA metabolism, such as mRNA splicing, stability, and translation, as well as other mRNA-independent processes, such as miRNA processing, protein sumoylation, and the nucleolar stress response. In this review, the structural features of SRSF1 are discussed as they relate to the intricate mechanism of splicing and the multiplicity of functions it performs. Similarly, a list of relevant alternatively spliced transcripts and SRSF1 interacting proteins is provided. Finally, emphasis is given to the deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers, and the complex mechanisms and pathways underlying SRSF1-mediated transformation. The accumulated knowledge about SRSF1 provides critical insight into the integral role it plays in maintaining cellular homeostasis and suggests new targets for anticancer therapy. Mol Cancer Res; 12(9); 1195-204. ©2014 AACR.

Figure 1. Modular domain structure of SRSF1

Primary structure of the SRSF1 protein highlighting the two N-terminal RNA recognition motifs (RRMs) and the C-terminal RS domain.

Figure 2. The multi-functional SR protein SRSF1

Splicing-dependent and independent functions of SRSF1 in the nucleus and cytoplasm. EJC-Exon Junction Complex; PTC-Premature Termination Codon; NFX1-Nuclear Exchange Factor 1; NPC-Nuclear Pore Complex.