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HIV-1 Infection Regulates Gene Expression by Altering Alternative Polyadenylation Through CPSF6 and CPSF5 Delocalization

ABSTRACT: HIV-1 viral core transport to the nucleus, an early infection event, triggers cleavage and polyadenylation specificity factor (CPSF)5 and CPSF6 to translocate from paraspeckles to nuclear speckles, forming puncta-like structures. CPSF5 and CPSF6 regulate alternative polyadenylation (APA), which governs approximately 70% of gene expression. APA alters the lengths of mRNA 3’-untranslated regions (3’-UTRs), which contain regulatory signals influencing RNA stability, localization, and function. We investigated whether HIV-1 infection–induced changes in CPSF5 and CPSF6 subcellular localization are accompanied by changes in cellular function. Using two independent methodologies to assess APA in human primary CD4+ T cells and cell lines, we found that HIV-1 infection regulates APA, dependent on the interaction of CPSF6 with the viral capsid, recapitulating the APA phenotype observed in CPSF6 knockout cells. Our study demonstrates that HIV-1 infection leverages the interaction between the viral capsid and CPSF6 to co-opt cellular processes, alter gene expression, and drive pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE313109 | GEO | 2025/12/10

REPOSITORIES: GEO

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			Action	DRS
		Other
	GSE313109_Samples_18_22_26_vs_17_21_25_APA_BBstats.txt.gz	Txt
	GSE313109_Samples_19_23_27_vs_17_21_25_APA_BBstats.txt.gz	Txt
	GSE313109_Samples_20_24_28_vs_17_21_25_APA_BBstats.txt.gz	Txt
	GSE313109_Samples_2_10_vs_1_9_APA_BBstats.txt.gz	Txt

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Project description:Cleavage factor I mammalian (CFIm) complex, composed of cleavage and polyadenylation specificity factor CPSF6, regulates alternative polyadenylation (APA). CPSF6 has a RS-like domain which plays role in protein -protein interactions. This interaction might have role in alternative polyadenylation site selection. The phosphorylation of RS- like domain might play role in protein -protein interaction and thus might have a role in alternative polyadenylation site selection. So we did mass specteroanalysis to analyse phosphorylation sites of RS-like domain of CPSF6.

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