Poster abstracts
Poster number 54 submitted by Tanner Hoog
Nucleolin Potentially Regulates G4-Duplex Equilibration During Ribosome Maturation Through Chaotropic Residues
Tanner G. Hoog (Department of Genetics, Cell Biology, and Development, University of Minnesota), Matthew R. Pawlak (Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota), Katarzyna P. Adamala (Department of Genetics, Cell Biology, and Development, University of Minnesota), Aaron E. Engelhart (Department of Genetics, Cell Biology, and Development, University of Minnesota)
Abstract:
Ribosomes are assembled in the nucleolus of cells where nucleolin, a nucleolus localizing protein, aids in ribosome maturation. Recently, it has been empirically shown that G-quadruplexes, a secondary structure of nucleic acid formed by the non-canonical base pairing of four guanines, fold on the ES27 segment of rRNA1. Additionally, nucleolin is known to bind and stabilize G-quadruplex conformation2. Given these overlapping findings, we seek to confirm the presence of G-quadruplex structures as the determinant of nucleolin mediated ribosomal biogenesis. Nucleolin’s binding domain is rich in arginine which has guanidinium groups, a chaotrope. In related work, we have observed that perchlorate, a Hofmeister chaotrope, selectively denatures duplexes relative to G-Quadruplexes. We are investigating whether nucleolin can modulate the G4-duplex equilibrium of rDNA (as has been shown to be the case in the anticancer drug quarfloxin3) or rRNA.
References:
1. Mestre-Fos, S. et al. G-quadruplexes in Human Ribosomal RNA. J. Mol. Biol. 1–16 (2019).
2. Lago, S., Tosoni, E., Nadai, M., Palumbo, M. & Richter, S. N. The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids. Biochim. Biophys. acta. Gen. Subj. 1861, 1371–1381 (2017).
3. Drygin, D. et al. Anticancer Activity of CX-3543: A Direct Inhibitor of rRNA Biogenesis. Cancer Res. 69, 7653–7661 (2009).
Keywords: Nucleolin, G-quadruplex, Ribosome Maturation