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Alternative intronic polyadenylation influences cancer metastasis and response to therapy

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE94375 | GEO | 2018/01/01

SECONDARY ACCESSION(S): PRJNA369518

REPOSITORIES: GEO

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Alternative intronic polyadenylation influences cancer metastasis and response to therapy [3'-seq]

Project description:We explored the impact of alternative polyadenylation regulation during tumor cell spreading.

2018-01-01 | GSE94373 | GEO

Alternative intronic polyadenylation influences cancer metastasis and response to therapy [CLIP-seq]

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Alternative intronic polyadenylation influences cancer metastasis and response to therapy

Project description:Alternative intronic polyadenylation influences cancer metastasis and response to therapy

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Alternative intronic polyadenylation generates the interleukin-6 trans-signaling inhibitor sgp130-E10.

Project description:Interleukin (IL)-6 signals via a receptor complex composed of the signal-transducing ?-receptor gp130 and the non-signaling membrane-bound or soluble IL-6 receptor ? (IL-6R, sIL-6R), which is referred to as classic and trans-signaling, respectively. IL-6 trans-signaling is functionally associated with the development of chronic inflammatory diseases and cancer. Soluble gp130 (sgp130) variants are natural inhibitors of trans-signaling. Differential splicing yields sgp130 isoforms. Here, we describe that alternative intronic polyadenylation in intron 10 of the gp130 transcript results in a novel mRNA coding for an sgp130 protein isoform (sgp130-E10) of 70-80 kDa. The sgp130-E10 protein was expressed in vivo in human peripheral blood mononuclear cells. To assess the biological activity of sgp130-E10, we expressed this variant as Fc-tagged fusion protein (sgp130-E10Fc). Recombinant sgp130-E10Fc binds to a complex of IL-6 and sIL-6R, but not to IL-6 alone, and specifically inhibits IL-6 trans-signaling. Thus, it might play an important role in the regulation of trans-signaling in vivo.

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Alternative polyadenylation alters protein dosage by switching between intronic and 3'UTR sites.

Project description:Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving the pre-mRNA at poly(A) sites that can lie within the 3' untranslated region (3'UTR), introns, or exons. Most studies focus on APA within the 3'UTR; however, here, we show that CPSF6 insufficiency alters protein levels and causes a developmental syndrome by deregulating APA throughout the transcript. In neonatal humans and zebrafish larvae, CPSF6 insufficiency shifts poly(A) site usage between the 3'UTR and internal sites in a pathway-specific manner. Genes associated with neuronal function undergo mostly intronic APA, reducing their expression, while genes associated with heart and skeletal function mostly undergo 3'UTR APA and are up-regulated. This suggests that, under healthy conditions, cells toggle between internal and 3'UTR APA to modulate protein expression.

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Compartment-specific and HuR-coordinated regulation of intronic polyadenylation isoforms by doxorubicin

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-09 | GSE180850 | GEO

An alternative polyadenylation mechanism coopted to the Arabidopsis RPP7 gene through intronic retrotransposon domestication.

Project description:Transposable elements (TEs) can drive evolution by creating genetic and epigenetic variation. Although examples of adaptive TE insertions are accumulating, proof that epigenetic information carried by such "domesticated" TEs has been coopted to control host gene function is still limited. We show that COPIA-R7, a TE inserted into the Arabidopsis thaliana disease resistance gene RPP7 recruited the histone mark H3K9me2 to this locus. H3K9me2 levels at COPIA-R7 affect the choice between two alternative RPP7 polyadenylation sites in the pre-mRNA and, thereby, influence the critical balance between RPP7-coding and non-RPP7-coding transcript isoforms. Function of RPP7 is fully dependent on high levels of H3K9me2 at COPIA-R7. We present a direct in vivo demonstration for cooption of a TE-associated histone mark to the epigenetic control of pre-mRNA processing and establish a unique mechanism for regulation of plant immune surveillance gene expression. Our results functionally link a histone mark to alternative polyadenylation and the balance between distinct transcript isoforms from a single gene.

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