Over the past decade, RNA-binding proteins (RBPs) have been increasingly recognized as important post-transcriptional regulators of gene expression governing molecular and cellular homeostasis. In fact, RBPs regulate multiple cellular processes such as survival, proliferation, migration, pluripotency, and immune cell function, as well as aid in the transition between cellular states in response to stimuli, e.g. during differentiation, cellular stress, or viral infection. In order to fulfil their cellular tasks and to influence the fate of few or many transcripts, RBPs interact with specific sequences or structural elements within their respective target RNA and thereby control splicing, polyadenylation, translation, localization, turnover, assembly and function of protein-RNA complexes and granules as well as editing and the incorporation of chemical modifications. Additional functions of RBPs in co-translational protein complex assembly, protein localization and protein folding have been suggested recently. Consequently, deregulated RBP activities can have severe effects on cellular homeostasis and are associated with human diseases, especially cancer.
Tumor formation is a multistep process during which normal cells evolve progressively to the neoplastic stage. These cells acquire particular capacities that enable them to become tumorigenic, the so-called hallmarks of cancer. Remarkable progress was made in the field of cancer research which led to a better understanding of these hallmark capabilities. Importantly, about 8% of human protein-coding genes have been assigned to the class of RBPs, yet only a small fraction of these have been functionally characterized in the context of cancer. Thus, molecular and mechanistic studies of RBPs in cancer are urgently needed to obtain a comprehensive understanding of the importance of RBP-controlled processes in cancer. This might lead to the identification of novel therapeutic targets and the development of innovative drugs that are able to interfere with the function of cancer-driving RBPs.
This Article Collection aims to bridge the gap between basic and clinical research in the field of RBPs in oncology. Hence, this collection will feature emerging molecular aspects of RNA and RBP biology as well as new methods to approach them. Furthermore, drug and target discovery strategies as well as therapeutic and diagnostic approaches focusing on RBPs for cancer detection and treatment will be highlighted. Furthermore, authors are invited to submit their original research as well as review articles describing recent progress in the prediction, identification, structural characterization, and measurement of RNA-protein interactions, the biochemical behavior and activities of RBPs as well as functional studies of novel and classical RBPs in human cancers.
The articles published in this collection will broaden our cellular and molecular understanding about the role of RBPs in cancer, pave the way towards the use of RBPs and RNA-protein interactions as diagnostic and therapeutic targets and shall stimulate novel precision cancer medicine efforts in this area.
Prof. Dr. Tony Gutschner joined the Martin Luther University Halle-Wittenberg as an Assistant Professor for RNA biology in 2017, after completing his PhD thesis at the German Cancer Research Center in Heidelberg (Germany) and a Postdoctoral Fellowship at the MD Anderson Cancer Center in Houston, Texas (USA). Research projects in his lab focus on cancer cell invasion and metastasis in order to develop novel therapeutic strategies. To this end, his team applies CRISPR-based genome editing and functional genomics in combination with cell and molecular biology techniques to identify key players, especially RNA-binding proteins and non-coding RNAs, and study their molecular mechanisms.
Prof. Dr. Stefan Hüttelmaier discovered a novel RNA binding protein (RBP), RAVER1, implicated in the interconnected regulation of alternative splicing and mRNA transport during his PhD. As a postdoctoral fellow in the Singer lab at the Albert Einstein College of Medicine, NYC (USA), he revealed a novel mechanism of spatially controlled ACTB translation by the RBP IGF2BP. Establishing his lab, he continued on characterizing the role of RBPs and cross-regulation by microRNAs in cancer. Currently, the main focus of his team is on characterizing the therapeutic target potential of oncofetal RBPs, primarily IGF2BPs, in cancer treatment.
Prof. Dr. Sven Diederichs discovered MALAT1 as one of the first long non-coding RNAs linked to cancer during his PhD thesis. Since then, he has investigated microRNAs and lncRNAs and unravelled their processing and function in complex with proteins. Most recently, together with Maiwen Caudron-Herger, he developed the "R-DeeP" approach to identify RNA-dependent proteins in cancer proteome-wide. Sven Diederichs is the head of the division "RNA Biology & Cancer" at the German Cancer Research Center (DKFz) in Heidelberg as well as a Professor of Cancer Research at the University of Freiburg.
Disclosure statement: Prof. Dr. Diederichs is co-owner of siTOOLs Biotech, Martinsried, Germany, without relation to this Article Collection. Prof. Dr. Gutschner and Prof. Dr. Hüttelmaier declare no conflict of interest.
