Alternative splicing factor or splicing factor‐2 plays a key role in intron retention of the endoglin gene during endothelial senescence

Blanco, Francisco J.; Bernabeu, Carmelo

doi:10.1111/j.1474-9726.2011.00727.x

Cited by 55 publications

(55 citation statements)

References 79 publications

(106 reference statements)

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“…In addition, we selected a core spliceosomal component of the U1 snRNP, snRNP‐U1–70K , and Psi , which associates with the U1‐snRNP and has been shown to play a role in courtship behavior in flies (Wang et al, 2016). We also selected SF2/dASF ( SRSF1 ) for functional analysis because SF2 has photoreceptor‐specific gene targets and has been implicated in aging (Blanco & Bernabeu, 2011, 2012; Gabut et al, 2007; Harries et al, 2011); however, SF2 expression was not significantly downregulated in aging photoreceptors in our analysis.…”

Section: Resultsmentioning

confidence: 99%

Proper splicing contributes to visual function in the aging Drosophila eye

et al. 2018

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Changes in splicing patterns are a characteristic of the aging transcriptome; however, it is unclear whether these age‐related changes in splicing facilitate the progressive functional decline that defines aging. In Drosophila, visual behavior declines with age and correlates with altered gene expression in photoreceptors, including downregulation of genes encoding splicing factors. Here, we characterized the significance of these age‐regulated splicing‐associated genes in both splicing and visual function. To do this, we identified differential splicing events in either the entire eye or photoreceptors of young and old flies. Intriguingly, aging photoreceptors show differential splicing of a large number of visual function genes. In addition, as shown previously for aging photoreceptors, aging eyes showed increased accumulation of circular RNAs, which result from noncanonical splicing events. To test whether proper splicing was necessary for visual behavior, we knocked down age‐regulated splicing factors in photoreceptors in young flies and examined phototaxis. Notably, many of the age‐regulated splicing factors tested were necessary for proper visual behavior. In addition, knockdown of individual splicing factors resulted in changes in both alternative splicing at age‐spliced genes and increased accumulation of circular RNAs. Together, these data suggest that cumulative decreases in splicing factor expression could contribute to the differential splicing, circular RNA accumulation, and defective visual behavior observed in aging photoreceptors.

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Section: Resultsmentioning

confidence: 99%

Proper splicing contributes to visual function in the aging Drosophila eye

et al. 2018

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“…Interestingly, S-endoglin expression is induced during senescence in ECs [93][94][95] and macrophages [96]. It is interesting that post-ischemic reperfusion is impaired in senescent individuals [67].…”

Section: What Is Endoglin?mentioning

confidence: 99%

“…In humans, S-endoglin has an intracellular domain that is 33 residues shorter than L-endoglin and lacks the PDZ binding motif ( Figure 5). One of the splicing factors involved in this intron retention process is serine-arginine splicing factor 1 (SRSF1 or ASF/SF2) [92]. Notably, ASF/SF2 is also involved in the selection of the splice site that yields proangiogenic VEGF isoforms, a process that is inhibited by TGF-β [90,93].…”

Section: What Is Endoglin?mentioning

confidence: 99%

The role of endoglin in post-ischemic revascularization

et al. 2016

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Following arterial occlusion, blood vessels respond by forming a new network of functional capillaries (angiogenesis), by re-organizing pre-existing capillaries through the recruitment of smooth muscle cells to generate new arteries (arteriogenesis) and by growing and remodeling pre-existing collateral arterioles into physiologically relevant arteries (collateral development). All these processes result in the recovery of organ perfusion. The importance of endoglin in post-occlusion reperfusion is sustained by several observations: i) endoglin expression is increased in vessels showing active angiogenesis/remodeling; ii) genetic endoglin haploinsufficiency in humans causes deficient angiogenesis; and iii) the reduction of endoglin expression by gene disruption or the administration of endoglin-neutralizing antibodies reduces angiogenesis and revascularization. However, the precise role of endoglin in the several processes associated with revascularization has not been completely elucidated and, in some cases, the function ascribed to endoglin by different authors is controversial. The purpose of this review is to organize in a critical way the information available for the role of endoglin in several phenomena (angiogenesis, arteriogenesis, and collateral development) associated with post-ischemic revascularization.

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“…The endoglin gene (ENG) is predominantly expressed as a long isoform (L-endoglin), but its pre-mRNA can be alternatively spliced by a mechanism of intron retention, yielding a less abundant form, known as short endoglin (S-endoglin). This intron retention is driven by the SRSF1 splicing factor, which physically competes with the minor spliceosome for the elimination of the last intron between exons 13 and 14 (Blanco and Bernabeu, 2011;Blanco and Bernabeu, 2012). When transcribed, the last intron of ENG bears an early stop codon that affects the open reading frame and truncates the mature protein at the cytoplasmic region (Blanco et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Expression of endoglin isoforms in the myeloid lineage and their role during aging and macrophage polarization

Aristorena¹,

Blanco²,

Casas-Engel³

et al. 2014

Journal of Cell Science

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Endoglin plays a crucial role in pathophysiological processes such as hereditary hemorrhagic telangiectasia (HHT), preeclampsia and cancer. Endoglin expression is upregulated during the monocyte-tomacrophage transition, but little is known about its regulation and function in these immune cells. Two different alternatively spliced isoforms of endoglin have been reported, L-endoglin and S-endoglin. Although L-endoglin is the predominant variant, here, we found that there was an increased expression of the S-endoglin isoform during senescence of the myeloid lineage in human and murine models. We performed a stable isotope labelling of amino acids in cell culture (SILAC) analysis of both L-endoglin and S-endoglin transfectants in the human promonocytic cell line U937. Analysis of differentially expressed protein clusters allowed the identification of cellular activities affected during aging. S-endoglin expression led to decreased cellular proliferation and a decreased survival response to granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced apoptosis, as well as increased oxidative stress. Gene expression and functional studies suggested that there was a nonredundant role for each endoglin isoform in monocyte biology. In addition, we found that S-endoglin impairs the monocytic differentiation into the pro-inflammatory M1 phenotype and contributes to the compromised status of macrophage functions during aging.

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Alternative splicing factor or splicing factor‐2 plays a key role in intron retention of the endoglin gene during endothelial senescence

Cited by 55 publications

References 79 publications

Proper splicing contributes to visual function in the aging Drosophila eye

Proper splicing contributes to visual function in the aging Drosophila eye

The role of endoglin in post-ischemic revascularization

Expression of endoglin isoforms in the myeloid lineage and their role during aging and macrophage polarization

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