Hanna Weferling

MD Student

Peter Mertens

Project Leader

This project investigates whether the RNA-bindings proteins (RBPs) act as molecular mediators linking extracellular nucleic acids with immunoglobulins in kidney diseases. Using human serum samples and complementary molecular interaction assays, the project aims to characterize RBP-associated extracellular RNA and investigate RBP:immunoglobulin interactions and their modulation by RNA/DNA.

Extracellular RNA and DNA are increasingly recognized as mediators of intercellular communication and immune regulation. However, extracellular nucleic acids are highly susceptible to degradation in the circulation, and the molecular mechanisms that protect and transport them in serum remain incompletely understood. There are RNA-binding proteins (RBPs) with established intracellular functions. Under conditions of cellular stress and inflammation, they can also occur extracellularly.

At the same time, extracellular RNA has been found to associate with immunoglobulins and circulating immune complexes in inflammatory and autoimmune diseases. However, it remains unclear whether RBPs, extracellular nucleic acids and immunoglobulins form interconnected molecular complexes in the circulation. This project therefore investigates the molecular interplay between extracellular RNA/DNA, RNA-binding proteins, and immunoglobulins in kidney diseases and to determine whether disease-associated interaction patterns can be identified.

The project comprises three complementary aims. First, RBP-associated extracellular RNA will be isolated and characterized using optimized serum RNA isolation workflows, eCLIP (enhanced CrossLinking and ImmunoPrecipitation) and Next-generation sequencing. Second, possible RBP:immunoglobulin interactions will be investigated in serum samples from different glomerular disease entities to determine whether their occurrence and composition differ between diseases. Third, biolayer interferometry will be used to quantitatively characterize RBP:RNA/DNA interactions and to investigate whether defined nucleic acids modulate RBP:immunoglobulin binding.