December 2024 - Lisa-Marie Appel

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Dr. Lisa-Marie Appel

MedUni Wien RESEARCHER OF THE MONTH December 2024

Regulation of gene expression at the transcriptional and post-transcriptional level is of critical importance for the establishment and maintenance of cellular identity. Dysregulation can contribute to developmental disorders and carcinogenesis. The protein domain SPOC is found in various proteins involved in gene expression regulation, including the human proteins PHF3, DIDO, RBM15 and SHARP. In this study, we show that the SPOC domains of all four of these proteins bind the phosphorylated C-terminal domain of RNA polymerase II. While PHF3 and DIDO are associated with the Pol II elongation complex to directly affect transcription, RBM15 and SHARP appear to coordinate the post-transcriptional fate of mRNA by recruiting m⁶A writer or reader proteins through their SPOC domains. The multivalent interactions of the SPOC proteins provide a crucial link between transcription and RNA metabolism and ensure precise regulation of gene expression.

Selected Literature

1. Appel LM, et al. The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators. Nat Commun. 2023;14(1):166. doi:10.1038/s41467-023-35853-1

2. Appel LM, et al. SPOC domain proteins in health and disease. Genes Dev. 2023;37(5-6):140-170. doi:10.1101/gad.350314.122

3. Appel LM, Franke V, Bruno M, Grishkovskaya I, et al. PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC. Nat Commun. 2021;12(1):6078. doi:10.1038/s41467-021-26360-2

4. Benedum J, et al. The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation. Nat Commun. 2023;14(1):7912. doi:10.1038/s41467-023-43724-y