Identification of G-quadruplex nucleic acid structures by high-throughput sequencing: A review

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 297, С. 139896 - 139896

Опубликована: Янв. 14, 2025

Язык: Английский

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The lncRNA DUBR is regulated by CTCF and coordinates chromatin landscape and gene expression in hematopoietic cells

Nucleic Acids Research, Год журнала: 2025, Номер 53(4)

Опубликована: Фев. 8, 2025

Abstract Master hematopoietic transcription factors (TFs) and long noncoding RNAs (lncRNAs) coordinate shaping lineage-specific gene expression programs during differentiation. The architectural protein CCCTC-binding factor (CTCF) has emerged as a pivotal regulator of in cell However, the relationship its regulatory effect CTCF on lncRNA genes hematopoiesis remain elusive. We demonstrated that constrains DUBRtranscription throughout erythroid DUBR is highly expressed human stem progenitor cells (HSPCs) but depleted erythroblasts. perturbation dysregulates hematopoietic-erythroid differentiation facilitates genome-wide activation elements. A genomic map RNA occupancy revealed associates with set involved regulating differentiation, including repressor HES1, which targets subset elements DUBR-dysregulated genes. Our results support role program by coordinating influencing their chromatin landscape.

Язык: Английский

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Xist RNA Dependent and Independent Mechanisms Regulate Dynamic X Chromosome Inactivation in B Lymphocytes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

X-Chromosome Inactivation (XCI) involves epigenetic pathways to equalize X-linked gene expression between female and male mammals. XCI is dynamic in B cells, as cytological enrichment of Xist RNA heterochromatic marks on the inactive X-chromosome (Xi) are absent naïve cells yet return following mitogenic stimulation. Here, we asked whether any histone present Xi required for their deposition retention We find that depleted H2AK119Ub H3K9me3 but enriched DNA methylation H3K27me3, which maintain an RNA-dependent memory XCI. Upon stimulation, Xist-independent H3K27me3 Xist-dependent modifications accumulate across with temporal spatial specificity. Our findings reveal importance RNA, integrity genes cell

Язык: Английский

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Isogenic comparison of Airn and Xist reveals core principles of Polycomb recruitment by lncRNAs

Molecular Cell, Год журнала: 2025, Номер 85(6), С. 1117 - 1133.e14

Опубликована: Март 1, 2025

Язык: Английский

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Re-analysis of CLAP data affirms PRC2 as an RNA binding protein

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 20, 2024

SUMMARY Using halo-tagged PRC2 and “CLAP” methodology, Guo et al. recently came to the conclusion that is not an RNA binding protein (RBP). They suggested previous findings are CLIP artifacts argue cannot play a direct role in regulation. Here, we perform re-analysis of authors’ raw datasets come contrary conclusions. First, CLAP demonstrates significant enrichment throughout transcriptome, including XIST’s Repeat A (RepA) motif. Second, our two methods yield similar outcomes, with both showing transcriptome. Furthermore, more peaks than SAF-A PTBP1. Additionally, contradicts CTCF YY1 RBP. The discrepancies may be attributable unconventional data normalization, determining significance, lack minus-tag input controls some experiments.

Язык: Английский

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PRC2-RNA interactions: Viewpoint from YongWoo Lee and Jeannie T. Lee

Molecular Cell, Год журнала: 2024, Номер 84(19), С. 3586 - 3592

Опубликована: Окт. 1, 2024

Язык: Английский

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PRC2-RNA interactions: Viewpoint from Tom Cech, Chen Davidovich, and Richard Jenner

Molecular Cell, Год журнала: 2024, Номер 84(19), С. 3593 - 3595

Опубликована: Окт. 1, 2024

Язык: Английский

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Diverse RNA Structures Induce PRC2 Dimerization and Inhibit Histone Methyltransferase Activity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 29, 2024

Methyltransferase PRC2 (Polycomb Repressive Complex 2) introduces histone H3K27 trimethylation, a repressive chromatin mark, to tune the differential expression of genes. is precisely regulated by accessory proteins, post-translational modifications and, notably, RNA. Research on PRC2-associated RNA has mostly focused tight-binding G-quadruplex (G4) RNAs, which inhibit enzymatic activity in vitro and cells. Our recent cryo-EM structure provided molecular mechanism for G4 inactivating via dimerization, but it remained unclear how diverse RNAs associate with regulate PRC2. Here, we show that single-stranded G-rich an atypical called pUG-fold unexpectedly also mediate near-identical dimerization resulting inhibition methyltransferase activity. The conformational flexibility arginine-rich loops within subunits EZH2 AEBP2 can accommodate secondary structures, protein-RNA protein-protein interfaces similar those observed previously Furthermore, address report failed detect living cells demonstrating insensitivity PRC2-RNA interaction photochemical crosslinking. results support significance RNA-mediated regulation showing this not limited single structure, consistent broad transcriptome containing many G-tract incapable folding into structures.

Язык: Английский

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A guide to RNA structure analysis and RNA‐targeting methods

FEBS Journal, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

RNAs are increasingly recognized as promising therapeutic targets, susceptible to modulation by strategies that include targeting with small molecules, antisense oligonucleotides, deoxyribozymes (DNAzymes), or CRISPR/Cas13. However, while drug development for proteins follows well-established paths rational design based on the accurate knowledge of their three-dimensional structure, RNA-targeting challenging since comprehensive RNA structures yet scarce and acquire. Numerous methods have been developed elucidate secondary structure RNAs, including X-ray crystallography, cryo-electron microscopy, nuclear magnetic resonance, SHAPE, DMS, bioinformatic methods, they often revealed flexible transcripts co-existing populations rather than single-defined structures. Thus, researchers aiming target face a critical decision: whether acquire detailed in advance adopt phenotypic screens sequence-based approaches independent structure. Still, even seem rely only nucleotide sequence (like oligonucleotides), may need information about accessibility compounds folded molecule. In this concise guide, we provide an overview interested RNAs: We start revisiting current methodologies defining then explore not require in-depth envision complementary expedite molecules combat disease.

Язык: Английский

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Recruitment of chromatin remodelers by XIST B-repeat region is variably dependent on HNRNPK

Human Molecular Genetics, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 26, 2024

Abstract X-chromosome inactivation is triggered by the long non-coding RNA XIST, whose structure characterized tandem repeats that modularly recruit different proteins and chromatin remodelers. Previously, we reported addition of mouse PID region to a transgene with human repeat regions A, F E (miniXIST; 5.1 kb) enabled binding HNRNPK also induction silencing recruitment H3K27me3, UbH2A H4K20me1, but only partially. As 680 bp so many features inactivation, hypothesized augmenting more or sequences rich in CCC motifs would allow us design short which was as effective Full XIST. Three new transgenes using domains backbone were tested for ability induce heterochromatic mark recruitment. The all human-derived BhB-BhB (4.9 good our previous miniXIST, suggesting these are equivalent region. A PID-PID (5.8 not statistically from XIST could be potentially used chromosome therapy. Adding BhB (BhB-PID, 5.4 had an intermediate efficacy compared other two transgenes, most important component number motifs, species origin. Finally, created heterozygous deletion observed disproportionate impact on reflecting complex roles inactivation.

Язык: Английский

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