RNA in formation and regulation of transcriptional condensates

Abstract

Macroscopic membraneless organelles containing RNA such as the nucleoli, germ granules, and the Cajal body have been known for decades. These biomolecular condensates are liquid-like bodies that can be formed by a phase transition. Recent evidence has revealed the presence of similar microscopic condensates associated with the transcription of genes. This brief article summarizes thoughts about the importance of condensates in the regulation of transcription and how RNA molecules, as components of such condensates, control the synthesis of RNA. Models and experimental data suggest that RNAs from enhancers facilitate the formation of a condensate that stabilizes the binding of transcription factors and accounts for a burst of transcription at the promoter. Termination of this burst is pictured as a nonequilibrium feedback loop where additional RNA destabilizes the condensate.

Keywords: RNA; condensate; intrinsically disordered domains; phase separation; transcription; transcription factors.

FIGURE 1.

RNA molecules produced by RNA polymerase I and RNA polymerase II. (A) Various types of RNA molecules synthesized by either RNA polymerase I or RNA polymerase II ([uaRNA] upstream antisense RNA, [eRNA] enhancer RNA, [lncRNA] long noncoding RNA, [rRNA] ribosomal RNA). (B) Properties of various RNA species—numbers and properties were derived from the following sources (McStay and Grummt 2008; Li et al. 2016; Schwalb et al. 2016; Hon et al. 2017; Frankish et al. 2019).

FIGURE 2.

A model for enhancer-driven condensate formation and gene activation. (A) Initial stages of transcription factor binding, which recruits chromatin remodelers, chromatin modifiers, and transcriptional coactivators. (B) Formation of transcriptional condensates by the concerted interaction of transcription factors, coactivators (BRD4, Mediator), RNA polymerase II, and modified chromatin. Compartmentalization and concentration of these factors promotes the assembly of the PIC.

FIGURE 3.

A nonequilibrium feedback mechanism for transcription mediated by RNA. Early stages of transcription produce low levels of RNA that help stimulate transcriptional condensate formation. Upon a burst of RNA synthesis during transcription elongation, the high levels of local RNA promote condensate dissolution. The stimulation and dissolution of transcriptional condensates by RNA define an auto-regulatory nonequilibrium feedback loop for transcription initiation and arrest.