DNMT1 inhibition by pUG-fold quadruplex RNA.

Autor:	Jansson-Fritzberg LI; BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA.; Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado 80303, USA.; Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA., Sousa CI; BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA.; Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado 80303, USA.; Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA., Smallegan MJ; BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA.; Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado 80303, USA., Song JJ; BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA.; Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado 80303, USA., Gooding AR; Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA., Kasinath V; Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado 80303, USA., Rinn JL; BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA.; Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado 80303, USA., Cech TR; BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA thomas.cech@colorado.edu.; Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado 80303, USA.; Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA.
Jazyk:	angličtina
Zdroj:	RNA (New York, N.Y.) [RNA] 2023 Mar; Vol. 29 (3), pp. 346-360. Date of Electronic Publication: 2022 Dec 27.
DOI:	10.1261/rna.079479.122
Abstrakt:	Aberrant DNA methylation is one of the earliest hallmarks of cancer. DNMT1 is responsible for methylating newly replicated DNA, but the precise regulation of DNMT1 to ensure faithful DNA methylation remains poorly understood. A link between RNA and chromatin-associated proteins has recently emerged, and several studies have shown that DNMT1 can be regulated by a variety of RNAs. In this study, we have confirmed that human DNMT1 indeed interacts with multiple RNAs, including its own nuclear mRNA. Unexpectedly, we found that DNMT1 exhibits a strong and specific affinity for GU-rich RNAs that form a pUG-fold, a noncanonical G-quadruplex. We find that pUG-fold-capable RNAs inhibit DNMT1 activity by inhibiting binding of hemimethylated DNA, and we additionally provide evidence for multiple RNA binding modes with DNMT1. Together, our data indicate that a human chromatin-associated protein binds to and is regulated by pUG-fold RNA. (© 2023 Jansson-Fritzberg et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)
Databáze:	MEDLINE
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