RNA in formation and regulation of transcriptional condensates

Abstract

Macrosopic 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 form by a phase transition. Recent evidence has revealed the presence of similar microscopic condensates associated with transcription of genes. This brief article summarizes thoughts about the importance of condensates in 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 non-equilibrium feedback loop where additional RNA destabilizes the condensate.

Transcriptional Regulation and Implications for Controlling Hox Gene Expression

“…The advent of new technologies for investigating the dynamics of interactions that underlie the activation of transcription are generating surprising findings. These observations challenge the widely postulated role of stable long-term enhancer promoter interactions and the notion of a single RNA polymerase with a small number of components regulating transcription [40][41][42][43][44][45][46][47][48][49]. New models suggest that dynamic condensates and mechanisms involving a series of rapid and complex interactions underlie the activation of transcription and the regulation of gene expression.…”

“…Progress has been made in the detection of transcriptional hubs containing a mediator complex using high resolution microscopy [ 43 , 164 ]. Recently, it has been observed that nascent transcripts themselves are in a feedback loop with the formation of transcriptional condensates; while nascent transcripts initially promote condensate formation, once they increase in numbers, they promote the dissolution of condensates [ 41 , 44 ]. This is relevant to the regulation of clustered Hox genes as it can be envisioned that enhancers and multiple gene promoters may reside within the same transcriptional hub or condensate for the coordinate regulation of their transcription.…”

“… Schematic of how the chromatin may loop to activate genes within the transcriptionally complex Hoxb gene cluster ( A ) Different loop confirmations envisioned for activation of specific genes within the Hoxb cluster, which contains several enhancer elements (such as DE, B4U and ENE) as well as coding and non-coding genes. ( B ) Inference [ 41 , 44 ] for how nascent Hoxb transcripts may promote condensate formation to increase nascent transcription, and subsequently, how an increased number of nascent transcripts may inhibit transcription by promoting condensate dissolution. Brown boxes at cluster edges depict boundary elements, blue and pink colored ovals depict coding genes and non-coding RNAs, respectively, and green ovals are RARE enhancers.…”

“…as well as coding and non-coding genes. (B) Inference [41,44] for how nascent Hoxb transcripts may promote condensate formation to increase nascent transcription, and subsequently, how an increased number of nascent transcripts may inhibit transcription by promoting condensate dissolution. Brown boxes at cluster edges depict boundary elements, blue and pink colored ovals depict coding genes and non-coding RNAs, respectively, and green ovals are RARE enhancers.…”

Nuclear RNA Exosome and Pervasive Transcription: Dual Sculptors of Genome Function

“…As the RNA exosome influences genome stability, it is important to understand how the RNA exosome controls the dynamics of nuclear meso-scale structures and controls compartmentation of biochemical reactions in the nuclei. Given that various RNA molecules targeted by the RNA exosome play important roles in intracellular liquid-liquid phase separation (LLPS), the biology of biomolecular condensate and LLPS may be intimately associated with the functions of the RNA exosome [121,122]. From this perspective, the RNA exosome may not only suppress deleterious effects of cryptic transcription but also facilitate functional innovation based on multivalent weak cooperative interaction, a hallmark of LLPS-type biological reactions, through effective compartmentation of biochemical reactions [123].…”