Stress responses revealing new modes of RNA-binding protein function

• Applicant: Professor Dr. Andreas Eckhard Kulozik, Ph.D.
• Subject Area: Biochemistry ; General Genetics and Functional Genome Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 498797126

Stress responses are key biological processes to protect cells from environmental insults. Based on the RNA-interactome capture technology invented and refined in the laboratory of one of the applicants, we have recently discovered the stress-responsive regulation of polyadenylated RNA-binding of the proteins SERBP1 and PCBP1. SERBP1 is known to associate with ribosomes that are silenced by stress. We have obtained additional experimental results indicating that SERBP1 switches from binding to polyadenylated RNA to binding to rRNA and supports eIF2α phosphorylation during the early phase of stress. PCBP1 is a known RNA-binding protein and a known iron-chaperoning protein. While these functions have been thought to be completely independent of each other, we have now discovered that PCBP1 RNA-binding is inhibited by oxidative stress, thus linking the RNA-binding and iron metabolism functions of PCBP1. Apparently, stress responses connect seemingly unrelated cellular functions of SERBP1 and PCBP by regulated RNA binding. The project proposed here will deeply explore these observations and provide mechanistic insight into unprecedented differential functions of RNA-binding proteins. Our work will define how regulated RNA binding contributes to the cellular responses under conditions of stress.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Matthias Hentze