Enhancer RNAs in transcriptional regulation: recent insights DOI Creative Commons
Qi Chen,

Yaxin Zeng,

Jinjin Kang

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Май 17, 2023

Enhancers are a class of cis-regulatory elements in the genome that instruct spatiotemporal transcriptional program. Last decade has witnessed an exploration non-coding transcripts pervasively transcribed from active enhancers diverse contexts, referred to as enhancer RNAs (eRNAs). Emerging evidence unequivocally suggests eRNAs important layer regulation. In this mini-review, we summarize well-established regulatory models for eRNA actions and highlight recent insights into structure chemical modifications underlying their functions. We also explore potential roles condensates.

Язык: Английский

Transcription regulation by long non-coding RNAs: mechanisms and disease relevance DOI
Jorge Ferrer, Nadya Dimitrova

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 25(5), С. 396 - 415

Опубликована: Янв. 19, 2024

Язык: Английский

Процитировано

97

Structural basis for inactivation of PRC2 by G-quadruplex RNA DOI
Jiarui Song, Anne R. Gooding, Wayne O. Hemphill

и другие.

Science, Год журнала: 2023, Номер 381(6664), С. 1331 - 1337

Опубликована: Сен. 21, 2023

Polycomb repressive complex 2 (PRC2) silences genes through trimethylation of histone H3K27. PRC2 associates with numerous precursor messenger RNAs (pre-mRNAs) and long noncoding (lncRNAs) a binding preference for G-quadruplex RNA. In this work, we present 3.3-Å-resolution cryo–electron microscopy structure bound to Notably, RNA mediates the dimerization by both protomers inducing protein interface composed two copies catalytic subunit EZH2, thereby blocking nucleosome DNA interaction H3 tail accessibility. Furthermore, an RNA-binding loop EZH2 facilitates handoff between DNA, another activity implicated in regulation We identified gain-of-function mutation that activates zebrafish. Our results reveal mechanisms RNA-mediated chromatin-modifying enzyme.

Язык: Английский

Процитировано

48

Denaturing purifications demonstrate that PRC2 and other widely reported chromatin proteins do not appear to bind directly to RNA in vivo DOI Creative Commons

Jimmy K. Guo,

Mario R. Blanco, Ward G. Walkup

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(7), С. 1271 - 1289.e12

Опубликована: Фев. 21, 2024

Polycomb repressive complex 2 (PRC2) is reported to bind many RNAs and has become a central player in reports of how long non-coding (lncRNAs) regulate gene expression. Yet, there growing discrepancy between the biochemical evidence supporting specific lncRNA-PRC2 interactions functional demonstrating that PRC2 often dispensable for lncRNA function. Here, we revisit RNA binding by show may not occur vivo. Using denaturing purification vivo crosslinked RNA-protein complexes human mouse cell lines, observe loss detectable chromatin-associated proteins previously (CTCF, YY1, others), despite accurately mapping bona fide RNA-binding sites across others (SPEN, TET2, others). Taken together, these results argue critical re-evaluation broad role orchestrate various chromatin regulatory mechanisms.

Язык: Английский

Процитировано

46

Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation DOI Creative Commons
Johannes Linder, Divyanshi Srivastava, Han Yuan

и другие.

Nature Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Язык: Английский

Процитировано

11

Intrinsically disordered regions as facilitators of the transcription factor target search DOI
Felix Jonas,

Yoav Navon,

Naama Barkai

и другие.

Nature Reviews Genetics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Язык: Английский

Процитировано

2

Pioneer factors: roles and their regulation in development DOI Creative Commons
Amandine Barral, Kenneth S. Zaret

Trends in Genetics, Год журнала: 2023, Номер 40(2), С. 134 - 148

Опубликована: Ноя. 7, 2023

Язык: Английский

Процитировано

39

Transcription regulation by biomolecular condensates DOI
Gaofeng Pei, Heankel Lyons, Pilong Li

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 8, 2024

Язык: Английский

Процитировано

16

Receptor-activated transcription factors and beyond: multiple modes of Smad2/3-dependent transmission of TGF-β signaling DOI Creative Commons
Keiji Miyazawa, Yuka Itoh, Hao Fu

и другие.

Journal of Biological Chemistry, Год журнала: 2024, Номер 300(5), С. 107256 - 107256

Опубликована: Апрель 2, 2024

Transforming growth factor β (TGF-β) is a pleiotropic cytokine that widely distributed throughout the body. Its receptor proteins, TGF-β type I and II receptors, are also ubiquitously expressed. Therefore, regulation of various signaling outputs in context-dependent manner critical issue this field. Smad proteins were originally identified as signal-activated transcription factors similar to signal transducer activator proteins. Smads activated by serine phosphorylation mediated intrinsic dual specificity kinases family, indicating receptor-restricted effector molecules downstream ligands family. have other functions addition transcriptional regulation, including post-transcriptional micro-RNA processing, pre-mRNA splicing, m6A methylation. Recent technical advances novel landscape Smad-dependent transduction, mitochondrial function without involving gene expression. receptor-activated act intracellular modulators with multiple modes function. In review, we discuss role beyond. We describe functional differences between Smad2 Smad3, two TGF-β, activin, myostatin, differentiation (GDF) 11, Nodal.

Язык: Английский

Процитировано

14

(Alternative) transcription start sites as regulators of RNA processing DOI Creative Commons

Carlos Alfonso-Gonzalez,

Valérie Hilgers

Trends in Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Март 1, 2024

Alternative transcription start site usage (ATSS) is a widespread regulatory strategy that enables genes to choose between multiple genomic loci for initiating transcription. This mechanism tightly controlled during development and often altered in disease states. In this review, we examine the growing evidence highlighting role sites (TSSs) regulation of mRNA isoform selection after We discuss how choice initiation influences RNA processing importance crosstalk cell identity organism function. also speculate on possible mechanisms underlying integration transcriptional post-transcriptional processes.

Язык: Английский

Процитировано

12

Structural basis of the Integrator complex assembly and association with transcription factors DOI Creative Commons
Michał Rażew, Angélique Fraudeau, Moritz M. Pfleiderer

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(13), С. 2542 - 2552.e5

Опубликована: Май 31, 2024

Integrator is a multi-subunit protein complex responsible for premature transcription termination of coding and non-coding RNAs. This achieved via two enzymatic activities, RNA endonuclease phosphatase, acting on the promoter-proximally paused polymerase Ⅱ (RNAPⅡ). Yet, it remains unclear how assembly recruitment are regulated what functions many its core subunits are. Here, we report structures human sub-complexes: INTS10/13/14/15 INTS5/8/10/15, an integrative model fully assembled bound to RNAPⅡ elongating (PEC). An in silico protein-protein interaction screen over 1,500 factors (TFs) identified ZNF655 as direct interacting partner INTS13 within Integrator. We propose wherein acts platform TFs that could modulate stability Integrator's association at specific loci regulate attenuation target genes.

Язык: Английский

Процитировано

12