SPOC domain proteins in health and disease

Abstract

Since it was first described >20 yr ago, the SPOC domain (Spen paralog and ortholog C-terminal domain) has been identified in many proteins all across eukaryotic species. SPOC-containing proteins regulate gene expression on various levels ranging from transcription to RNA processing, modification, export, and stability, as well as X-chromosome inactivation. Their manifold roles in controlling transcriptional output implicate them in a plethora of developmental processes, and their misregulation is often associated with cancer. Here, we provide an overview of the biophysical properties of the SPOC domain and its interaction with phosphorylated binding partners, the phylogenetic origin of SPOC domain proteins, the diverse functions of mammalian SPOC proteins and their homologs, the mechanisms by which they regulate differentiation and development, and their roles in cancer.

Exploring the role of m 6 A writer RBM15 in cancer: a systematic review

“…The RRM domain is highly prevalent in eukaryotes and plays an essential role in post-transcriptional splicing, translation, nuclear export, and mRNA stabilization ( 45 , 46 ). The SPOC domain, characterized by seven β-strands and four α-helices ( Figure 1C ), has been demonstrated to influence several facets of mammalian gene expression, encompassing transcription, RNA modification, RNA export, and X-chromosome inactivation ( 47 , 48 ). Recent discovery revealed that the SPOC domain serves as a phosphoserine binding module, with conserved motifs on its surface specifically recognizing the C-terminal domain (CTD) phosphorylation tag of RNA polymerase II (RNA Pol II) ( 42 ).…”

“…Recent discovery revealed that the SPOC domain serves as a phosphoserine binding module, with conserved motifs on its surface specifically recognizing the C-terminal domain (CTD) phosphorylation tag of RNA polymerase II (RNA Pol II) ( 42 ). RBM15 SPOC domain was shown to predominantly regulate m 6 A modification and enhance mRNA stability by binding to the m 6 A reader ( 48 ). Furthermore, the SPOC domain engages with a range of factors, including histone lysine methyltransferase SETD1B, nuclear RNA export factor 1 (NXF1), and DEAD-box protein 5 (DBP5), thereby participating in RNA transcription, export, and RNA-related metabolism ( 35 , 49 , 50 ).…”