Natural antisense transcripts as versatile regulators of gene expression

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: April 17, 2024

Language: Английский

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Revisiting CPSF30-mediated alternative polyadenylation in Arabidopsis thaliana

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0319180 - e0319180

Published: Feb. 24, 2025

Alternative polyadenylation (APA) is an important contributor to the regulation of gene expression in plants. One subunit complex that cleaves and polyadenylates mRNAs nucleus, CPSF30 (for 30 kD mammalian Cleavage Polyadenylation Specificity Factor), has been implicated a wide-ranging network regulatory events. plays roles root development, flowering time, response biotic abiotic stresses. also conduit links cellular signaling RNA modification with alternative processing events transcriptional dynamics. While much known about its plants, questions remain regarding connections between CPSF30-mediated APA downstream lead specific phenotypic outcomes. To address these, we conducted detailed analysis poly(A) site usage mutant. Our results corroborate earlier reports link distinctive cis element (AAUAAA) present 10-30 nts upstream some, but not all, plant pre-mRNAs. Interestingly, our reveal shift mutants deficient CPSF30, resulting cleavage at location motifs similar AAUAAA. Importantly, CPSF30-associated had best small impact on mRNA functionality. These necessitate formulation new hypotheses for mechanisms by which influences physiological processes.

Language: Английский

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Intronic alternative polyadenylation in MdMYB1 regulates fruit coloration in apple

Plant Science, Journal Year: 2025, Volume and Issue: unknown, P. 112450 - 112450

Published: Feb. 1, 2025

Language: Английский

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Functional inhibition of core spliceosomal machinery activates intronic premature cleavage and polyadenylation of pre-mRNAs

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115376 - 115376

Published: Feb. 27, 2025

Highlights•U6/U2 snRNP inhibits global intronic PCPA (premature cleavage and polyadenylation)•U6/U2 regulates mRNA 3′-UTR (untranslated region) length for a subset of genes•Intronic is positively regulated by the 3′ processing activatorSummaryThe catalytic role U6 in pre-mRNA splicing has been well established. In this study, we utilize an antisense morpholino oligonucleotide (AMO) specifically targeting sites snRNA to achieve functional knockdown HeLa cells. The data show significant increase premature polyadenylation (PCPA) events, similar those observed with U1 AMO treatment, as demonstrated 3′-seq analysis. Mechanistically, provide evidence that AMO-mediated inhibition might be driving force application another specific U2 results effects. Together our recently published findings demonstrate inhibitory effect U4 on PCPA, highlight critical suppressing support model which may compete each other within introns during co-transcriptional processing.Graphical abstract

Language: Английский

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The alternative polyadenylation regulator CFIm25 promotes macrophage differentiation and activates the NF-κB pathway

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 28, 2025

Abstract Background Macrophages are required for development and tissue repair protect against microbial attacks. In response to external signals, monocytes differentiate into macrophages, but our knowledge of changes that promote this transition at the level mRNA processing, in particular polyadenylation, needs advancement if it is inform new disease treatments. Here, we identify CFIm25, a well-documented regulator poly(A) site choice, as novel mediator macrophage differentiation. Methods CFIm25 expression was analyzed differentiating primary human monocytic cell lines. Overexpression depletion experiments were performed assess CFIm25’s role differentiation, NF-κB signaling, alternative polyadenylation (APA). 3’ end-focused sequencing conducted use genes involved differentiation function. Cell cycle markers, pathway components, their targets examined. The signaling further evaluated through chemical inhibition knockdown regulators. Results showed striking increase upon suggesting promotes process. Indeed, overexpression during amplified acquisition characteristics caused an earlier slowing cycle, hallmark transition, along with APA-mediated downregulation cyclin D1. plays major maturation mRNAs null, TBL1XR1, NFKB1, all positive regulators underwent 3’UTR shortening, coupled corresponding proteins. also elevated phosphorylation NF-κB-p65 transcription activator, produced p21, Bcl-XL, ICAM1 TNF-α, resulted greater resistance inhibition. Knockdown Tables 2 TBL1XR1 CFIm25-overexpressing cells attenuated these effects, reinforcing mechanistic link between CFIm25-regulated APA activation. Conversely, hindered led lengthening TAB2, UTRs. Conclusions Our study establishes key operates coordinated control progression signaling. This linkage processing immune function expands understanding regulating

Language: Английский

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Novel insights into the Leishmania infantum transcriptome diversity of protein-coding and non-coding sequences in both stages of parasite development using Nanopore direct RNA sequencing

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Background: Leishmania relies on posttranscriptional control to regulate gene expression. Protein-coding genes are synthesised as polycistronic precursors that processed into individual mRNAs by coupled trans-splicing adding the spliced leader (SL) RNA 5'-end of all transcripts and 3' cleavage-polyadenylation. Here, we employ Nanopore direct sequencing (DRS) combined with Illumina RNA-Seq comprehensively interrogate transcriptomes Leishmania infantum developmental stages at single-molecule resolution. Results: Analysis DRS full-length reads poly(A)+-enriched from L. enabled us precisely determine primary SL poly(A) sites for 52% protein-coding accurately define their 5'- 3'-end boundaries length UTRs. We observed a higher diversity per transcript than sites. The frequency site was ~ 64.2%, whereas incidence 24%, most having additional nearby. Alternative polyadenylation detected in 11–13% transcripts, which 28% were developmentally regulated. Similarly, 26.5% different between differentially expressed. Our analysis confirmed motifs ‘[C/A/T] A|G’ being associated 94.8% cleavage better defined genomic context polyadenylation. Further, uncovered multiple processing events occurring mostly within long 3'UTRs, leading formation non-coding RNAs (lncRNAs). transcriptome expresses rich repertoire 1,825 lncRNAs, 98% not previously annotated absent major may be specific infantum. Generally, these lncRNAs exhibit distinct expression patterns 3'UTRs they derived, several regulated, representing 27% stage-regulated transcriptome. Protein prediction tools mass-spectrometry revealed 7.6% have limited potential. Conclusions: This is first comprehensive transcriptomic using DRS. findings advance knowledge existing datasets provide new insights complexity dynamics sequences throughout parasite development.

Language: Английский

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IGF2BP3 recruits NUDT21 to regulate SPTBN1 alternative polyadenylation and drive ovarian cancer progression

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: April 29, 2025

Ovarian cancer (OC) is one of the deadliest gynecological malignancies. As prevalent post-transcriptional regulation, alternative polyadenylation (APA) plays a crucial role in various tumors. Here we identify that APA regulator NUDT21 upregulated OC and promotes malignant progression. We further demonstrate IGF2BP3 interacts with NUDT21, which suggests m6A modification could regulate processing. Mechanistically, IGF2BP3, recognizing m6A-modified site intron 32 SPTBN1, recruits to promote usage SPTBN1 proximal (PAS), thus increasing generation short transcripts cells. Intriguingly, long variant demonstrates tumor-suppressive properties, whereas enhances oncogenic activity OC. Subsequently, illustrate isoform inhibits tumor growth metastasis by binding CDK1 blocking G2/M phase cell cycle. In conclusion, this study uncovers previously unrecognized regulatory mechanism OC, provide potential therapeutic strategies for

Language: Английский

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Roles for epithelial integrin α3β1 in regulation of the microenvironment during normal and pathological tissue remodeling

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 326(5), P. C1308 - C1319

Published: March 18, 2024

Integrin receptors for the extracellular matrix activate intracellular signaling pathways that are critical tissue development, homeostasis, and regeneration/repair, their loss or dysregulation contributes to many developmental defects pathologies. This review will focus on remodeling roles integrin α3β1, a receptor laminins found in basement membranes (BMs) underlie epithelial cell layers. As paradigm, we discuss literature supports role α3β1 promoting ability of epidermal keratinocytes modify microenvironment during skin wound healing, tumorigenesis. Preclinical clinical studies have shown this depends largely govern keratinocyte's repertoire secreted proteins, "secretome," including

Language: Английский

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Transcriptomic analysis reveals regulation of adipogenesis via long non-coding RNA, alternative splicing, and alternative polyadenylation

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 23, 2024

Obesity is characterized by dysregulated adipogenesis that leads to increased number and/or size of adipocytes. Understanding the molecular mechanisms governing therefore key designing therapeutic interventions against obesity. In our study, we analyzed 3'-end sequencing data generated from human preadipocytes and adipocytes, as well previously published RNA-seq datasets, elucidate regulation via long non-coding RNA (lncRNA), alternative splicing (AS) polyadenylation (APA). We discovered lncRNAs have not been but may be regulators white adipogenesis. also detected 100 AS events and, using motif enrichment analysis, identified binding proteins (RBPs) could mediate exon skipping—the most prevalent event. addition, show usage poly(A) sites in introns or 3'-UTRs genes isoform diversity, which can significant biological consequences on differentiation efficiency. RBPs modulate APA defined how 3'-UTR regulate gene expression through gain loss specific microRNA sites. Taken together, bioinformatics-based analysis reveals potential avenues for obesity manipulation lncRNA levels profile mRNA isoforms polyadenylation.

Language: Английский

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A developmental mechanism to regulate alternative polyadenylation in an adult stem cell lineage

Genes & Development, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 7, 2024

Alternative cleavage and polyadenylation (APA) often results in production of mRNA isoforms with either longer or shorter 3′ UTRs from the same genetic locus, potentially impacting translation, localization, stability. Developmentally regulated APA can thus make major contributions to cell type-specific gene expression programs as cells differentiate. During Drosophila spermatogenesis, ∼500 genes undergo when proliferating spermatogonia differentiate into spermatocytes, producing transcripts shortened UTRs, leading profound stage-specific changes proteins expressed. The molecular mechanisms that specify usage upstream sites spermatocytes are key understanding state. Here, we show upregulation PCF11 Cbc, two components factor II (CFII), orchestrates during spermatogenesis. Knockdown cbc caused dysregulation APA, many normally cleaved at a proximal site now their distal site, spermatogonia. Forced overexpression CFII switched some used spermatocytes. Our findings reveal developmental mechanism where specific factors direct selected genes.

Language: Английский

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