RNA-Mediated Feedback Control of Transcriptional Condensates

Biomolecular Condensates and Cancer

“…RNA molecules play regulatory roles in diverse biomolecular condensates, including the nucleolus, transcriptional condensates, cotranscriptional splicing condensates, nuclear speckles, paraspeckles, and stress granules (Fay and Anderson, 2018;Guo et al, 2019;Henninger et al, 2021;Roden and Gladfelter, 2020;Sabari, 2020;Strom and Brangwynne, 2019). Condensates are formed by an ensemble of low-affinity molecular interactions, including electrostatic interactions, and RNA can be a powerful regulator of condensates that are formed and maintained by these forces (Banani et al, 2017;Elbaum-Garfinkle et al, 2015;Henninger et al, 2021;Maharana et al, 2018;Peran and Mittag, 2020;Shin and Brangwynne, 2017;Zhang et al, 2015a). The functions of the vast majority of ncRNA species expressed in cells are not known, and it seems likely that many will be found to play regulatory roles in diverse condensates.…”

“…ll super-enhancer transcriptional condensate suggests that condensate alterations are in play (Sabari et al, 2018;Shin et al, 2018;Wei et al, 2020). ncRNA molecules are components of well-studied biomolecular condensates, where they have various regulatory functions (Clemson et al, 2009;Daneshvar et al, 2020;Henninger et al, 2021;Yamazaki et al, 2018). In cancer cells, ncRNAs are overexpressed (MALAT1, HOTAIR, SRA, CCAT2, LincRNAROR, lncRNA-ATB, LncTCF7, SCHLAP1, treRNA, ZEB2-AS1, UCA1), underexpressed (LET, DRAIC, EGOT, GAS5, MEG3, NBAT-1, NKILA, PCAT), and post-transcriptionally modified (Barbieri and Kouzarides, 2020;.…”

Phase separation of RNA-binding protein promotes polymerase engagement and transcription

“…Recently, it was reported that RNA stimulates transcription factor condensates at low levels but dissolves these condensates at high levels 44,45 . A phase-separation model of RNA-mediated feedback control appears attractive to explain features of transcription processes 45,46 . However, this hypothesis remains inconclusive as the key link that connects RNA to the transcriptional machinery with a characteristic DNA-binding activity is still missing.…”

Co-condensation of proteins with single- and double-stranded DNA

“…An important class of such membrane-less compartments are formed by the condensation of proteins and other components in dynamic assemblies called biomolecular condensates (Hyman, Weber and Jülicher, 2014;Aguzzi and Altmeyer, 2016;Banani et al, 2017). Biomolecular condensates increase the local concentration of their components, which can lead to substantially accelerated biochemical reactions (Li et al, 2012;Hernández-Vega et al, 2017). Condensates that form beyond a saturation concentration can buffer the cellular concentration of molecules while at the same time clamping the concentration of phaseseparated components inside (Klosin et al, 2020).…”

“…Furthermore, transcriptional condensates are dense and dynamic assemblies of transcription factors, associated proteins, DNA and RNA. Such condensates have been suggested to play an important role in the generation of transcriptional hubs that could coordinate the expression of several genes and mediate enhancer function (Cho et al ., 2018; Sabari et al ., 2018; Guo et al ., 2019; Henninger et al ., 2021). Recently it was shown that a pioneer transcription factor can form co-condensates together with DNA in vitro (Quail et al ., 2020).…”