Roles of RNA Modifications in Diverse Cellular Functions DOI Creative Commons
Emma Wilkinson, Yan‐Hong Cui, Yu‐Ying He

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: March 8, 2022

Chemical modifications of RNA molecules regulate both metabolism and fate. The deposition function these are mediated by the actions writer, reader, eraser proteins. At cellular level, several processes including cell death, proliferation, senescence, differentiation, migration, metabolism, autophagy, DNA damage response, liquid-liquid phase separation. Emerging evidence demonstrates that play active roles in physiology etiology multiple diseases due to their pervasive functions. Here, we will summarize recent advances regulatory functional role functions, emphasizing context-specific mammalian systems. As m

Language: Английский

RNA in formation and regulation of transcriptional condensates DOI Open Access
Phillip A. Sharp, Arup K. Chakraborty, Jonathan E. Henninger

et al.

RNA, Journal Year: 2021, Volume and Issue: 28(1), P. 52 - 57

Published: Nov. 12, 2021

Macroscopic membraneless organelles containing RNA such as the nucleoli, germ granules, and 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 presence of similar microscopic associated with transcription genes. This brief article summarizes thoughts about importance in regulation how molecules, components condensates, control synthesis RNA. Models experimental data suggest RNAs from enhancers facilitate formation condensate stabilizes binding factors accounts burst at promoter. Termination this is pictured nonequilibrium feedback loop where additional destabilizes condensate.

Language: Английский

Citations

96
The multifaceted effects of YTHDC1-mediated nuclear m6A recognition DOI
Jocelyn Widagdo, Victor Anggono, Justin Wong

et al.

Trends in Genetics, Journal Year: 2021, Volume and Issue: 38(4), P. 325 - 332

Published: Dec. 14, 2021

Language: Английский

Citations

71
The epitranscriptome toolbox DOI Creative Commons
Sharon Moshitch-Moshkovitz, Dan Dominissini,

Gideon Rechavi

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 764 - 776

Published: March 1, 2022

Language: Английский

Citations

69
Biomolecular condensates: new opportunities for drug discovery and RNA therapeutics DOI Creative Commons
Brooke A. Conti, Mariano Oppikofer

Trends in Pharmacological Sciences, Journal Year: 2022, Volume and Issue: 43(10), P. 820 - 837

Published: Aug. 23, 2022

Numerous examples now exist where biomolecular condensates are mechanistically linked to disease.Small-molecule drugs used in the clinic today can interact with condensates, whether intended or not, possibly affecting their pharmacology.Recent clinical success has demonstrated utility of RNA therapeutics help patients and propelled interest this field.Endogenous is a key constituent both physiological pathological potential link between prospective emerging.Understanding interaction small molecules may improve drug discovery process. Biomolecular organize cellular functions absence membranes. These membraneless organelles form through liquid–liquid phase separation coalescing proteins into well-defined, yet dynamic, structures distinct from surrounding milieu. disease-causing processes which could impact several ways. First, disruption seeded by mutated RNAs provide new opportunities treat disease. Second, be leveraged tackle difficult-to-drug targets lacking binding pockets whose function depends on separation. Third, condensate-resident display unexpected pharmacology. We discuss therapeutics, leveraging concrete examples, towards novel opportunities. Membraneless organelles, support compartmentalization spatiotemporal regulation biochemical activities inside cells [1.Shin Y. Brangwynne C.P. Liquid condensation cell physiology disease.Science. 2017; 357: eaaf4382Crossref PubMed Scopus (1287) Google Scholar, 2.Lyon A.S. et al.A framework for understanding across scales.Nat. Rev. Mol. Cell Biol. 2021; 22: 215-235Crossref (121) 3.Banani S.F. al.Biomolecular condensates: organizers biochemistry.Nat. 18: 285-298Crossref (1891) Scholar]. (hereafter condensates), term coined represent coalescence biomolecules (see Glossary) like [3.Banani Scholar], functional, nonstoichiometric, dynamic assemblies that, membrane-bound create subcellular environments but lack enclosing membranes import/export machinery. Dynamism discriminators aggregates (Box 1). While alternative models [4.Darzacq X. Tjian R. 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Lett. 126258101Crossref (5) This allows quantitative composition cells, supports interesting properties, flux out reactions take place Scholar].Finally, only generate macromolecular instance, loading static active concentration volumes motors many ways analogous formed condensates. Certain Finally, Recent developments field have illuminated disease, action currently [6.Banani al.Genetic variation associated dysregulation disease.Dev. 57: 1776-1788.e8Abstract (15) Scholar,7.Kilgore H.R. Young R.A. Learning chemical grammar Chem. (Published online June 27, 2022)https://doi.org/10.1038/s41589-022-01046-yCrossref highlight emerging trends likely influence discovery, particularly RNA-based therapeutics. mechanistic dysregulated how therapeutic approaches. also aid modulation modalities, along pharmacology existing therapies. aim readers forward-looking insights integrates evolving fields deliver patients. Intracellular borrowing concepts polymer science, boundaries effectively substitute lipid permitting diffusion phases (Figure 1A ) Scholar,3.Banani Scholar,8.Riback energy reduction caused (by satisfying attractive repulsive intermolecular forces) opposes entropy-driven mixing all components. In simplest form, leads two-phase assumes different depending constituents' concentration, strength, valency, parameters temperature pH. result liquid, freely-fusing assemblies; present continuum 1B) Scholar,9.Alberti forces leading RNA–RNA, protein–RNA, DNA–DNA, protein–DNA, protein–protein interactions, structured domains (e.g., modules) intrinsically disordered regions (IDRs) [10.Sabari B.R. nucleus.Trends Biochem. Sci. 45: 961-977Abstract (102) 1C). [12.Molliex A. low complexity stress granule assembly drives fibrillization.Cell. 2015; 163: 123-133Abstract (1231) [13.Van Treeck B. self-assembly defining transcriptome.Proc. Natl. Acad. 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Language: Английский

Citations

60
Roles of RNA Modifications in Diverse Cellular Functions DOI Creative Commons
Emma Wilkinson, Yan‐Hong Cui, Yu‐Ying He

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: March 8, 2022

Chemical modifications of RNA molecules regulate both metabolism and fate. The deposition function these are mediated by the actions writer, reader, eraser proteins. At cellular level, several processes including cell death, proliferation, senescence, differentiation, migration, metabolism, autophagy, DNA damage response, liquid-liquid phase separation. Emerging evidence demonstrates that play active roles in physiology etiology multiple diseases due to their pervasive functions. Here, we will summarize recent advances regulatory functional role functions, emphasizing context-specific mammalian systems. As m

Language: Английский

Citations

57