The simplest proteins are built from a single chain of amino acids that fold into an energetically stable, three-dimensional structure. Many complex proteins, however, contain multiple domains, sub-structures that can fold into a stable compact structure independent of the rest of the protein. During the course of evolution, large proteins with complex functions have been created by the assembly of domains in a combinatorial, modular manner. One such domain is called SPOC (Spen orthologue and paralogue C-terminal), which is found in six human proteins. In 2021, the lab of Dea Slade demonstrated that the SPOC domain of a protein called PHF3 recognizes phosphorylated residues in the C-terminal domain (CTD) of RNA polymerase II, thereby linking PHF3 to the regulation of gene expression. Whether CTD domain binding is unique to PHF3 or if other SPOC domains possess the same ability has, however, so far not been addressed.
The Slade lab has now teamed up with scientists from the Max Delbrück Center (Berlin) along with the groups of Kristina Djinovic Carugo and Bojan Zagrovic at the Max Perutz Labs to study the remaining five known SPOC proteins in humans. “We found that these SPOC domains also bind to the C-terminal domain of RNA polymerase II. SPOC is therefore a universal CTD reader, but SPOC domain-containing proteins exhibit different binding specificities”, explains Dea Slade. By recognizing differentially phosphorylated CTD residues, these proteins regulate transcription at different stages.
Supported by the mass spectrometry facility at the Max Perutz Labs, the team investigated potential binding partners of SPOC proteins apart from RNA polymerase II. They discovered that RBM15 and SHARP, members of the SPEN family, interact with readers and writers of N6-methyladenosine (m6A), one of the most abundant RNA modifications, which plays a key role in regulating RNA stability. “RBM15 was previously characterized as a component of the m6A complex, but it was unclear how it recruits the complex onto RNA. We show that it is the RBM15 SPOC domain that brings the whole complex to the target RNA”, says Dea Slade. In this way, transcription is directly linked to the regulation of RNA stability. However, many questions regarding the fine tuning of the interactions between SPOC proteins and their partners remain. “SPOC proteins share binding partners with similar binding affinities, raising the question of how these interactions are regulated in the cell and what the functional consequences of switching between binding partners are”, concludes Dea Slade.
Lisa-Marie Appel, Vedran Franke, Johannes Benedum, Irina Grishkovskaya, Xué Strobl, Anton Polyansky, Gregor Ammann, Sebastian Platzer, Andrea Neudolt, Anna Wunder, Lena Walch, Stefanie Kaiser, Bojan Zagrovic, Kristina Djinovic-Carugo, Altuna Akalin, Dea Slade: The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators. Nature Communications 2022
https://www.nature.com/articles/s41467-023-35853-1
18th Microsymposium on RNA Biology
The „Microsymposium on RNA Biology“ is an international conference that brings together young scientists, junior and senior group leaders, and company representatives from all over the world to present and discuss their latest findings in the exciting field of small RNAs and beyond. The Microsymposium was founded in 2005 and has established itself as the major small RNA meeting in Europe. It is organized by the four research institutions IMBA, IMP, GMI and the Max Perutz Labs as well as by the RNA community of the Vienna BioCenter.
Nickel impact on human health, from bacterial infections to cancer
Multiscale plant bioimaging using advanced microscopy
Parthenogenesis, cryptobiosis, and the survival in extreme environmental conditions
Evading ageing: Mitochondrial and proteostatic adaptations in oocytes
Genomes in Rhodnius prolixus symbiotic system
Stem cells, immune evasion and metastasis in colorectal cancer
Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
Title to be announced
New players in an old pathway: biology of methanogens of the TACK superphylum
Shaping morphogen gradients: from molecules to tissues and back
Title to be announced
Studying stressed cells by in situ structural biology
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Arbuscular mycorrhiza development and function
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
The unanticipated roles of PICIs and phages in bacterial evolution
Chemical targeting of subcellular protein localization
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Connections between carbon and nitrogen cycling in the ocean
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
From Roads to Rivers? Occurrence and environmental fate of tire and road wear particles and of tire-related chemicals
FENS 2024 Satellite event: Home cage behavior monitoring at the interface of animal welfare and neuroscience
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced