Novel RNA-mediated regulatory roles of the human hnRNP L proteins

• Applicant: Professor Dr. Albrecht Bindereif
• Subject Area: General Genetics and Functional Genome Biology ; Biochemistry ; Cell Biology
• Term: from 2008 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 80033308

The heterogenous nuclear ribonucleoprotein (hnRNP) L acts as a multifunctional RNA-binding protein with four RNA-recognition domains (RRMs), recognizing CA-rich RNA elements and activating or repressing alternative splicing in a position-dependent manner. As we have shown for CD45 alternative splicing in human B-cells, hnRNP L sometimes collaborates with hnRNP-like, a closely related paralog with the same domain organization. In addition, hnRNP L can regulate RNA stability, and our recent transcriptome-wide iCLIP analysis revealed global widespread binding in 3'-untranslated regions (3'UTRs) of mRNAs. On this basis we plan to characterize novel RNA-mediated roles of the hnRNP L proteins: First, we will address the potential role of hnRNP L in binding within 3'UTRs of mRNAs, focussing on competitive hnRNP L/microRNA binding, in particular its relevance for mRNA stability and translation. Second, we will extend our iCLIP approach to the hnRNP L-like paralog, to comprehensively analyze the hnRNP L/L-like cooperation in human B-cells. These genome-wide in vivo binding data will be complemented by an in vitro SELEX-Seq approach, focussing on the differential RNA-binding activities of the hnRNP L proteins and the combinatorial RNA recognition of their four RRMs. Third, we will explore a novel, potential function of the hnRNP L paralogs, binding to circular RNA sponges; we plan both to search for natural examples and to design artificial, hnRNP L/LL-specific circRNA sponges.

• DFG Programme: Research Grants