RNA-Protein Complexes and Cell Proliferation

The characterisation of RNA-binding proteins

The analysis of RNA-protein complexes is central to elucidating the complex molecular networks that govern cellular processes. With the increasing recognition of their importance, proteins that interact directly with RNA have attracted growing interest. However, the comprehensive but specific identification of such RNA-binding proteins (RBPs) and the dissection of their functions in association with RNA remain major challenges in the field of RNA biology.
To further deepen our knowledge of RBPs, several proteome-wide strategies have been developed to identify RBPs in different species. Thus, a large number of studies have provided catalogs of experimentally identified as well as predicted RBP candidates. The rapid evolution of the field has led to an accumulation of isolated datasets, hampering both accessibility and comparability. Furthermore, tools for linking RBPs to cellular pathways and functions were lacking. Driven by our own research and as a service to the scientific community, we developed RBP2GO, a comprehensive database of all available proteome-wide datasets for RBPs across 13 species, providing a catalog of 22552 RBP candidates (RBP2GO.DKFZ.de). It not only includes data on RBP interaction partners but also provides information on related biological processes, molecular functions, and cellular components.
RBP2GO provides a user-friendly web interface with a scoring system that reflects the potential of RBP candidates to be bona fide RBPs. The RBP2GO advanced search provides users with options to navigate through the interconnected datasets to promote and stimulate new research directions.
Ongoing projects are currently refining the list of RBPs by incorporating information on RNA-binding domains (RBDs) and RNA-related protein families. These multi-purpose analyses aim to refine the extensive list of RBP candidates and to provide a list of high confidence RBPs, based on a scoring system.

Related publications:

• Wassmer et al. 2024 Nucleic Acids Research 52(13):7504-7522
• Caudron-Herger et al. 2021 Nucleic Acids Research 49:D425-436 

RNA-binding proteins in breast and ovarian cancers (RB²OC)

Cancer is a complex disease that involves the successive establishment of dysfunctions in multiple key cellular processes leading to characteristics hallmarks such as sustaining proliferative signaling, resisting cell death and enabling replicative immortality. While breast cancer is the most prevalent cancer in women, ovarian cancer has one of the poorest prognoses among all cancer types. Mutations in BRCA1 and BRCA2 represent major risk factors for both breast and ovarian cancer. While hereditary breast and ovarian cancer represent ∼10%–20% of the disease fraction in the population, only ∼10% of hereditary cases are due to mutations in BRCA1/2, suggesting additional, yet unknown risk factors to be identified.

RNA-binding proteins play important roles in the regulation of gene expression through the regulation of mRNA splicing, stability and translation, thereby affecting the development, progression and treatment response of cancer diseases. Recent advances in RNA biology have led to the identification of an increasing number of RNA-binding proteins. Based on our data, RNA-binding proteins such as TIAR and TPX2 are important for cell cycle control and genomic stability, and connected to BRCA proteins. RB²OC will explore their respective role and relationship in both cancer types. In particular, we will examine the potential diagnostic and prognostic value of TIAR and TPX2 expression levels, assess their relation to DNA repair pathways through mutational landscape analysis, and address the impact of TIAR/TPX2 on the sensitivity of breast cancer and ovarian cancer to specific DNA damage inhibitors. Using an interdisciplinary approach, we will determine the role of TIAR and TPX2 dysfunction as putative drivers of breast cancer and ovarian cancer pathogenesis.

Collaboration:

• Prof. Dr. Dr. Georg Stoecklin
• Prof. Dr. med. Frederik Marmé
• Prof. Dr. Benedikt Brors 

Funding:

• DKFZ Hector Cancer Institute

R-DeeP3 provides the proteome-wide screening results for RNA-dependent protein complexes from unsynchronized HeLa S3 and A549 lung cancer cells as well as synchronized HeLa cells in mitosis and interphase. In addition, R-DeeP3 offers options for the comparison of all the datasets and for the download of the results. 

R-DeeP provides the proteome-wide screening results for RNA-dependent protein complexes based on our paper in Molecular Cell 2019. It contains the full dataset from HeLa S3 cells and offers additional search options for protein complexes plus RBPs from different sources.