The Splicing Factor SRSF1 as a Marker for Endothelial Senescence

Blanco, Francisco J.; Bernabéu, Carmelo

doi:10.3389/fphys.2012.00054

Cited by 44 publications

(37 citation statements)

References 63 publications

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“…Downregulation of splicing factor SRSF3 induces an alternatively spliced isoform of p53 that promotes cellular senescence [298]. Senescence-associated stress signals result in the cytoplasmic accumulation of several splicing factors such as SRSF1 in endothelial cells [299], their shuttling being controlled by their phosphorylation status and by RanBP2 (Nup358), constituting the cytoplasmic filaments of NPC [300]. Two splicing factors, SRSF1 and 6, exihibit opposite effect on the progerin production by HGPS fibroblasts [301].…”

Section: Dna Replication Transcription Repair and Epigenetic Defectmentioning

confidence: 99%

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cau

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Harhouri

et al. 2014

Seminars in Cell & Developmental Biology

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Lamin A-related progeroid syndromes are genetically determined, extremely rare and severe. In the past ten years, our knowledge and perspectives for these diseases has widely progressed, through the progressive dissection of their pathophysiological mechanisms leading to precocious and accelerated aging, from the genes mutations discovery until therapeutic trials in affected children. A-type lamins are major actors in several structural and functional activities at the nuclear periphery, as they are major components of the nuclear lamina. However, while this is usually poorly considered, they also play a key role within the rest of the nucleoplasm, whose defects are related to cell senescence. Although nuclear shape and nuclear envelope deformities are obvious and visible events, nuclear matrix disorganization and abnormal composition certainly represent the most important causes of cell defects with dramatic pathological consequences. Therefore, lamin-associated diseases should be better referred as laminopathies instead of envelopathies, this later being too restrictive, considering neither the key structural and functional roles of soluble lamins in the entire nucleoplasm, nor the nuclear matrix contribution to the pathophysiology of lamin-associated disorders and in particular in defective lamin A processing-associated aging diseases. Based on both our understanding of pathophysiological mechanisms and the biological and clinical consequences of progeria and related diseases, therapeutic trials have been conducted in patients and were terminated less than 10 years after the gene discovery, a quite fast issue for a genetic disease. Pharmacological drugs have been repurposed and used to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA in progeria. To date, none of them may be considered as a cure for progeria and these clinical strategies were essentially designed toward reducing a subset of the most dramatic and morbid features associated to progeria. New therapeutic strategies under study, in particular targeting the protein expression pathway at the mRNA level, have shown a remarkable efficacy both in vitro in cells and in vivo in mice models. Strategies intending to clear the toxic accumulated proteins from the nucleus are also under evaluation. However, although exceedingly rare, improving our knowledge of genetic progeroid syndromes and searching for innovative and efficient therapies in these syndromes is of paramount importance as, even before they can be used to save lives, they may significantly (i) expand the affected childrens' lifespan and preserve their quality of life; (ii) improve our understanding of aging-related disorders and other more common diseases; and (iii) expand our fundamental knowledge of physiological aging and its links with major physiological processes such as those involved in oncogenesis.

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Section: Dna Replication Transcription Repair and Epigenetic Defectmentioning

confidence: 99%

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cau

Navarro

Harhouri

et al. 2014

Seminars in Cell & Developmental Biology

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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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“…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%

“…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 Splicing Factor SRSF1 as a Marker for Endothelial Senescence

Cited by 44 publications

References 63 publications

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Proper splicing contributes to visual function in the aging Drosophila eye

The role of endoglin in post-ischemic revascularization

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