New overview of RNA binding molecules and their role in kidney disease

03.11.2021 | TopNews Prof. Dr. Thomas Benzing Prof. Dr. Roman-Ulrich Müller

RNA binding molecules have various roles in the cell

Animated RNA strong | ©Shutterstock MattLphotography

Roman-Ulrich Müller and his team introduce new concept to kidney research | Publication in Nature Reviews Nephrology

Research on the interaction between proteins is a focus of many groups both in basic and medical science. Much less is known about the contribution of RNA-protein interactions to human disease. RNA-binding proteins (RBPs) are involved in every step of the life cycle of an RNA. However, RNA can also regulate protein function vice-versa. With the number of known RBPs exceeding over 1000 in the human genome, these proteins, have a major impact on cellular biology clearly indicating their importance for human disease.

“We have worked the past years on identifying novel RBPs in kidney cells as well as their modulation by pathways important to kidney health and disease. Our findings and also the lack of an overview was the motivation to prepare our paper“, said Lisa Seufert, the first author of the study.

“Our review provides the first concise and exhaustive overview of the role of RBPs in kidney disease. We point out how the growing knowledge on RNA-protein interactions may have an important contribution to novel therapeutic strategies which are often lacking regarding pathologies of the kidney”, said Müller.

RBPs in the kidney

  • have been shown to have roles in tubular and glomerular kidney diseases, including acute kidney injury (AKI), chronic kidney disease, kidney fibrosis, polycystic kidney disease (PKD), diabetic kidney disease and glomerulonephritis.
  • can have both protective and pathogenic roles in kidney diseases; for example, two of the best studied RBPs — HuR and YBX1 — ameliorate damage in AKI but promote kidney fibrosis.
  • their role in kidney disorders is conserved throughout evolution; for example, mutations in BICC1 lead to a cystic phenotype of the Malpigian tubules in Drosophila melanogaster and are associated with PKD in vertebrates.
  • environmental changes that are associated with renal pathophysiology, such as hypo-osmolality or hypoxia, can modulate RNA–protein interactions.
  • RNA–protein interactions can be inhibited and are potential therapeutic targets for various kidney diseases.