The role of RNAs in biomolecular condensation of leukemia fusion oncoproteins

Biomolecular condensation of macromolecules in cells creates membraneless microenvironments that enable specific biological processes. Biomolecular condensates contain proteins and RNA, and various biochemical and biophysical parameters influence the propensity of these macromolecules to phase separate. Likewise, biomolecular condensation was proposed to represent an important mechanism in the oncogenic function of NUP98-fusion proteins, which are found in aggressive forms of pediatric acute myeloid leukemia (AML). In these fusions, the intrinsically disordered region in the NUP98 N-terminus is essential for their biomolecular condensation and for the induction of leukemia-associated transcriptional programs, but the role of RNAs in this process is not known. While some RNAs were proposed to have direct roles in transcriptional regulation, others may exert structural roles that are important to establish and/or maintain interactions between proteins, RNA and chromatin. We aim to investigate the contribution of cellular RNAs to biomolecular condensation of the oncogenic NUP98::KDM5A fusion protein.

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Zentrum für Biologische Wissenschaften