The molecular chaperone ALYREF promotes R-loop resolution and maintains genome stability DOI Creative Commons
Jay Bhandari, Cristina Guillén-Mendoza,

Kathryn Primrose Banks

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107996 - 107996

Published: Nov. 1, 2024

Unscheduled R-loops usually cause DNA damage and replication stress, are therefore a major threat to genome stability. Several RNA processing factors, including the conserved THO complex its associated DNA-RNA helicase UAP56, prevent R-loop accumulation in cells. Here we investigate function of ALYREF, an export adapter with UAP56 complex, regulation. We demonstrate that purified ALYREF promotes UAP56-mediated dissociation vitro, this stimulation is dependent on interaction R-loops. Importantly, show binds hybrids Consistently, depletion causes R-loop-mediated instability propose apart from known role metabolism export, key cellular co-regulator, which stimulates UAP56-driven resolution unscheduled during transcription.

Language: Английский

The hidden weavers: A review of DNA/RNA R-loops in stem cell biology and therapeutic potential DOI
Xu Chen,

Zizhao Mai,

Yucheng Zheng

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 297, P. 139895 - 139895

Published: Jan. 14, 2025

Language: Английский

Citations

0
Transcription: friend or foe of genome stability DOI
Emmanuel Compe, Donata Orioli

FEBS Letters, Journal Year: 2025, Volume and Issue: 599(2), P. 143 - 146

Published: Jan. 1, 2025

Language: Английский

Citations

0
R-loop homeostasis in genome dynamics, gene expression and development DOI
Paula Aguilera, Andrés Aguilera

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102325 - 102325

Published: March 4, 2025

Language: Английский

Citations

0
Transcription-Coupled Repair and R-Loop Crosstalk in Genome Stability DOI Open Access

Jeseok Jeon,

Tae‐Hong Kang

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3744 - 3744

Published: April 16, 2025

Transcription-coupled repair (TCR) and R-loops are two interrelated processes critical to the maintenance of genome stability during transcription. TCR, a specialized sub-pathway nucleotide excision repair, rapidly removes transcription-blocking lesions from transcribed strand active genes, thereby safeguarding transcription fidelity cellular homeostasis. In contrast, R-loops, RNA–DNA hybrid structures formed co-transcriptionally, play not only regulatory roles in gene expression replication but can also contribute instability when persistently accumulated. Recent experimental evidence has revealed dynamic crosstalk between TCR R-loop resolution pathways. This review highlights current molecular insights into biology, discusses impact their crosstalk, explores emerging therapeutic strategies aimed at optimizing DNA reducing disease risk conditions such as cancer neurodegenerative disorders.

Language: Английский

Citations

0
RNA-Mediated Non-Mendelian Inheritance in Mice: The Power of Memory DOI Creative Commons
Minoo Rassoulzadegan

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 605 - 605

Published: April 21, 2025

The mouse genome is transcribed at different rates in both directions from the newly formed after fertilization. During embryonic genomic activation (EGA/ZGA), first RNA metabolism creates heterogeneity between blastomeres. Indeed, ZGA-dependent maternal degradation crucial to regulate gene expression and enable initiation acquisition of full developmental competence. Subsequently, new genome, addition mRNAs, a wide range regulatory ncRNAs are also transcribed. Regulatory (non-coding RNAs) have profoundly influenced fields ranging biology RNA-mediated non-Mendelian inheritance, exhibiting sequence-specific functions. To date, database cataloging ncRNA not exhaustive, but their high sequence diversity, length low level can vary within same depending on environmental conditions, making understanding functions often ambiguous. during transcription control, cellular content varies continuously. This phenomenon observed genetically identical organisms studied—bacteria, flies, plants mammals—due changes rates, therefore, it impacts memory. Importantly, experimental data regarding simple modification RNAs levels by microinjection into fertilized eggs suggest that they certainly play driving role establishing transmitting information. idea here that, even stable transcripts rapidly significantly response changes, initiated transcriptional variations thus altering

Language: Английский

Citations

0
Pathological R-loops in bacteria from engineered expression of endogenous antisense RNAs whose synthesis is ordinarily terminated by Rho DOI Creative Commons
Apuratha Pandiyan,

Jillella Mallikarjun,

Himanshi Maheshwari

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(20), P. 12438 - 12455

Published: Sept. 12, 2024

In many bacteria, the essential factors Rho and NusG mediate termination of synthesis nascent transcripts (including antisense RNAs) that are not being simultaneously translated. It has been proposed in Rho's absence toxic RNA-DNA hybrids (R-loops) may be generated from untranslated transcripts, genome-wide mapping studies Escherichia coli have identified putative loci R-loop formation more than 100 endogenous synthesized only a Rho-deficient strain. Here we provide evidence engineered expression wild-type E. several such individual regions on plasmid or chromosome generates R-loops that, an RNase H-modulated manner, serve to disrupt genome integrity. inhibition was associated with increased prevalence also Xanthomonas oryzae pv. Caulobacter crescentus. Our results confirm role bacterial genera for prevention pervasive yet cryptic transcripts. Engineered R-looped useful both site-specific impediments chromosomal replication mechanisms their resolution.

Language: Английский

Citations

1
Different alterations in mRNP composition trigger an increase in harmful R-loops DOI Creative Commons
José Antonio Mérida-Cerro, Guillaume Chevreux, Benoı̂t Palancade

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Abstract Understanding how the assembly of nascent mRNA into a ribonucleoprotein (mRNP) influences R-loop homeostasis is crucial for gaining insight cellular mechanisms that prevent genome instability. Here, we identify three RNA-binding proteins, Rie1, Rim4 and She2, whose stoichiometry important to limit accumulation and, thus, DNA damage. Interestingly, She2 are overrepresented in mRNPs assembled absence THO. In addition, found an excess Dis3 impairs exosome function, promoting R-loops, particularly from non-coding RNAs, which cause genomic Our results indicate mRNP precise process that, when perturbed by changes availability different RBPs or causes R-loop-mediated damage cell. These may help understand mechanism promotes cancer, as several overexpressed types tumors. Author summary R-loops three-stranded structures formed DNA-RNA hybrid displaced ssDNA. The damages genome, highlighting need their tight regulation. One prevents formation co-transcriptional RNA messenger (mRNP). study reveals biogenesis highly sensitive perturbations. Not only components, but also overexpression specific proteins (RBPs) persistence unstable transcripts, significantly stresses assembly, resulting consequent involved number neurodegenerative diseases importance understanding processes mitigate accumulation.

Language: Английский

Citations

0
The molecular chaperone ALYREF promotes R-loop resolution and maintains genome stability DOI Creative Commons
Jay Bhandari, Cristina Guillén-Mendoza,

Kathryn Primrose Banks

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107996 - 107996

Published: Nov. 1, 2024

Unscheduled R-loops usually cause DNA damage and replication stress, are therefore a major threat to genome stability. Several RNA processing factors, including the conserved THO complex its associated DNA-RNA helicase UAP56, prevent R-loop accumulation in cells. Here we investigate function of ALYREF, an export adapter with UAP56 complex, regulation. We demonstrate that purified ALYREF promotes UAP56-mediated dissociation vitro, this stimulation is dependent on interaction R-loops. Importantly, show binds hybrids Consistently, depletion causes R-loop-mediated instability propose apart from known role metabolism export, key cellular co-regulator, which stimulates UAP56-driven resolution unscheduled during transcription.

Language: Английский

Citations

0