Alternative Polyadenylation in Cancer: Molecular Mechanisms and Clinical Application DOI
Ying Zhang,

Zikun Huang,

Weiqing Lu

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 206, P. 104599 - 104599

Published: Dec. 18, 2024

Language: Английский

2′-O-methylation at internal sites on mRNA promotes mRNA stability DOI
Yanqiang Li,

Yi Yang,

Xinlei Gao

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(12), P. 2320 - 2336.e6

Published: June 1, 2024

Language: Английский

Citations

15
Transcription regulation by biomolecular condensates DOI
Gaofeng Pei, Heankel Lyons, Pilong Li

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Language: Английский

Citations

11
HIV-1 usurps mixed-charge domain-dependent CPSF6 phase separation for higher-order capsid binding, nuclear entry and viral DNA integration DOI Creative Commons
Sooin Jang, Gregory J. Bedwell, Satya P. Singh

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 25, 2024

Abstract HIV-1 integration favors nuclear speckle (NS)-proximal chromatin and viral infection induces the formation of capsid-dependent CPSF6 condensates that colocalize with speckles (NSs). Although displays liquid-liquid phase separation (LLPS) activity in vitro, contributions its different intrinsically disordered regions, which includes a central prion-like domain (PrLD) capsid binding FG motif C-terminal mixed-charge (MCD), to LLPS remain unclear. Herein, we determined PrLD MCD both contribute vitro. Akin mutant CPSF6, cells expressing MCD-deleted uncharacteristically arrested at rim. While heterologous MCDs effectively substituted for function during infection, Arg-Ser domains from related SR proteins were largely ineffective. wildtype displayed similar affinities, imparted LLPS-dependent higher-order co-aggregation capsids vitro cellulo. NS depletion reduced puncta without significantly affecting into NS-proximal chromatin, appending onto protein partially restored virus penetration targeting knockout cells. We conclude MCD-dependent condensation underlies post-nuclear incursion DNA pathogenesis.

Language: Английский

Citations

8
Downregulation of CPSF6 leads to global mRNA 3’ UTR shortening and enhanced antiviral immune responses DOI Creative Commons
Yong Ge, Jingrong Huang, Rong Chen

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(2), P. e1012061 - e1012061

Published: Feb. 28, 2024

Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates mRNA isoforms with alternative 3’ untranslated regions (3’ UTRs). Our previous study has revealed the global UTR shortening host mRNAs through APA upon viral infection. However, how dynamic changes in landscape occur infection remains largely unknown. Here we further found that, reduced protein abundance CPSF6, one core processing factors, promotes usage proximal poly(A) sites (pPASs) many immune related genes macrophages and fibroblasts Shortening these transcripts may improve their stability translation efficiency, leading to promotion type I IFN (IFN-I) signalling-based antiviral responses. In addition, dysregulated expression CPSF6 also observed physiological pathological conditions, especially various infections cancers. Thus, dynamics regulated by can fine-tune response as well responses other cellular stresses maintain tissue homeostasis, which represent novel regulatory for immunity.

Language: Английский

Citations

7
HIV-1-induced translocation of CPSF6 to biomolecular condensates DOI

Katarzyna Bialas,

Felipe Diaz‐Griffero

Trends in Microbiology, Journal Year: 2024, Volume and Issue: 32(8), P. 781 - 790

Published: Jan. 23, 2024

Language: Английский

Citations

4
Exploring vimentin's role in breast cancer via PICK1 alternative polyadenylation and the miR‐615‐3p‐PICK1 interaction DOI Creative Commons

Xinyan Jia,

Lujing Shao,

Hong Quan

et al.

BioFactors, Journal Year: 2025, Volume and Issue: 51(1)

Published: Jan. 1, 2025

Abstract Breast cancer continues to be a major health issue for women worldwide, with vimentin (VIM) identified as crucial factor in its progression due role cell migration and the epithelial‐to‐mesenchymal transition (EMT). This study focuses on elucidating VIM's regulatory mechanisms miR‐615‐3p/PICK1 axis. Utilizing 4T1 breast model, we first used RNA‐seq proteomics investigate changes APA of PICK1 following VIM knockout (KO). These high‐throughput analyses aimed uncover underlying transcriptional proteomic alterations associated influence cells. profiling revealed significant KO, suggesting novel mechanism by which regulates progression. Validation experiments confirmed that KO affects miR‐615‐3p‐PICK1 axis, miR‐615‐3p's regulation being contingent upon PICK1. findings highlight complex interplay between VIM, miR‐615‐3p, behavior. reveals axis through APA, revealing key Opened up new avenues targeted therapy, focus regulating interaction miR‐615‐3p‐PICK1.

Language: Английский

Citations

0
Liquid-liquid phase separation in cell physiology and cancer biology: recent advances and therapeutic implications DOI Creative Commons
Ziyuan Huang, Zimeng Liu,

Lieqian Chen

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 31, 2025

Liquid-liquid phase separation (LLPS) is a pivotal biophysical phenomenon that plays critical role in cellular organization and has garnered significant attention the fields of molecular mechanism pathophysiology cancer. This dynamic process involves spontaneous segregation biomolecules, primarily proteins nucleic acids, into condensed, liquid-like droplets under specific conditions. LLPS drives formation biomolecular condensates, which are crucial for various functions. Increasing evidences link alterations to onset progression diseases, particularly review explores diverse roles cancer, highlighting its underlying mechanisms far-reaching implications. We examine how dysregulated contributes cancer development by influencing key processes such as genomic instability, metabolism, immune evasion. Furthermore, we discuss emerging therapeutic strategies aimed at modulating LLPS, underscoring their potential revolutionize treatment.

Language: Английский

Citations

0
CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells DOI Creative Commons
Kiel T. Tietz, Braedan M. McCluskey, Conor R. Miller

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115211 - 115211

Published: Jan. 1, 2025

Language: Английский

Citations

0
E3 ligase SYVN1-mediated polyubiquitination of CPSF6 promotes alternative polyadenylation and antivirus effects of macrophages DOI Creative Commons

Xin Lu,

Chao Liu, Runze Wu

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(2), P. 115276 - 115276

Published: Feb. 1, 2025

Transcriptome-wide alternative polyadenylation (APA) is involved in both innate and adaptive immune responses of cells. Downregulation the CPSF6 protein, one 3' end-processing factors, mediates APA macrophages with to virus infection plays an important role its anti-virus effect. However, signaling pathway molecular mechanism underlying downregulation protein remain elusive. Here, we found that MAVS triggers nuclear import E3 ligase SYVN1 mediated by NUP153 response vesicular stomatitis infection. Then, catalyzes K48-linked polyubiquitination CPSF6, resulting degradation via proteasome then transcriptome-wide effects. Our results identify antiviral regulation based on ubiquitination modification which may serve as a target for developing interventions.

Language: Английский

Citations

0
m6A-mediated regulation of CPSF6 by METTL3 promotes oxaliplatin resistance in colorectal cancer through enhanced glycolysis DOI
Chengxing Wang, Weijun Liang,

Jietao Zhong

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: 130, P. 111676 - 111676

Published: Feb. 25, 2025

Language: Английский

Citations

0