# The Chromaverse Is Colored by Triplexes Formed Through the Interactions of Noncoding RNAs with HNPRNPU, TP53, AGO, REL Proteins, Intrinsically-Disordered Regions, and Flipons

## TL;DR

The paper explores triplexes formed by RNA-DNA interactions and their role in regulating chromatin structure and retroelements.

## Contribution

The study introduces AlphaFold V3 models of triplex interactions and their role in chromatin regulation and retroelement control.

## Key findings

- TRXs form through RNA-DNA Hoogsteen base pairing and involve various RNA classes.
- TRXs interact with proteins like HMGB1, HNRNPU, TP53, and AGO.
- TRXs regulate retroelements and influence chromatin boundaries and disordered protein folding.

## Abstract

Triplexes (TRX) are a class of flipons that can form due to the interaction of RNA with B-DNA. While many proteins have been proposed to bind triplexes, structural models of these interactions do not exist. Here, I present AlphaFold V3 (AF3) models that reveal interactions between the high-mobility group protein B1 (HMGB1), HNRNPU (SAF-A), TP53, ARGONAUTE (AGO), and REL domain proteins. The TRXs result from the sequence-specific docking of RNAs to DNA via Hoogsteen base pairing. The RNA and DNA strands in apolar TRX are oriented in the opposite 5′ to 3′ direction, while copolar TRX have RNA and DNA strands pointing in the same 5′ to 3′ direction. TRXs can incorporate different RNA classes, including long noncoding RNAs (lncRNAs), short RNAs, such as miRNAs, piRNAs, and tRNAs, nascent RNA fragments, and non-canonical base triplets. Many pathways regulated by TRX formation have evolved to constrain retroelements (EREs), which are both an existential threat to the host and a source of genotypic variation. TRXs help set the boundaries of active chromatin, repressing the expression of most EREs, while depending on other flipons to modulate cellular programs. The TRXs help nucleate folding of intrinsically disordered proteins.