DNMT1 inhibition by pUG-fold quadruplex RNA. Journal Article uri icon

Overview

abstract

  • 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.

publication date

  • March 1, 2023

has subject area

has restriction

  • bronze

Date in CU Experts

  • January 3, 2023 7:42 AM

Full Author List

  • Jansson-Fritzberg LI; Sousa CI; Smallegan MJ; Song JJ; Gooding AR; Kasinath V; Rinn JL; Cech TR

author count

  • 8

published in

Other Profiles

Electronic International Standard Serial Number (EISSN)

  • 1469-9001

Additional Document Info

start page

  • 346

end page

  • 360

volume

  • 29

issue

  • 3