Pre‐mRNA splicing modulations in senescence

Meshorer, Eran; Soreq, Hermona

doi:10.1046/j.1474-9728.2002.00005.x

Cited by 79 publications

(81 citation statements)

References 46 publications

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“…By controlling and modifying the expression patterns of stress-related proteins as an adaptation strategy, they can modify relevant transcripts from their usually expressed forms to specially adapted ones. 4 The PFC long-lasting overexpression of SC35 in close association to that of AChE-R is consistent with this hypothesis. SC35 is also intensively expressed in the developing neocortex, primarily in progenitor cells as they pass through the mitotic phase of the cell cycle and express AChE-R.…”

Section: Sc35 In Long-term Stress Responsessupporting

confidence: 77%

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SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA

et al. 2005

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Long-lasting alternative splicing of neuronal acetylcholinesterase (AChE) pre-mRNA occurs during neuronal development and following stress, altering synaptic properties. To explore the corresponding molecular events, we sought to identify mRNAs encoding for abundant splicing factors in the prefrontal cortex (PFC) following stress. Here we show elevated levels of the splicing factor SC35 in stressed as compared with naïve mice. In cotransfections of COS-1 and HEK293 cells with an AChE minigene allowing 3 0 splice variations, SC35 facilitated a shift from the primary AChE-S to the stress-induced AChE-R variant, while ASF/SF2 caused the opposite effect. Transfection with chimeric constructs comprising of SC35 and ASF/SF2 RRM/RS domains identified the SC35 RRM as responsible for AChE mRNA's alternative splicing. In poststress PFC neurons, increased SC35 mRNA and protein levels coincided with selective increase in AChE-R mRNA. In the developing mouse embryo, cortical progenitor cells in the ventricular zone displayed transient SC35 elevation concomitant with dominance of AChE-R over AChE-S mRNA. Finally, transgenic mice overexpressing human AChE-R, but not those overexpressing AChE-S, showed significant elevation in neuronal SC35 levels, suggesting a reciprocal reinforcement process. Together, these findings point to an interactive relationship of SC35 with cholinergic signals in the long-lasting consequences of stress on nervous system plasticity and development. Molecular Psychiatry (2005) 10, 985-997.

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Section: Sc35 In Long-term Stress Responsessupporting

confidence: 77%

“…Long-lasting changes in alternative splicing in the nervous system 1,2 are associated with disease, 3 aging and trauma, 4 as well as with cortical neurogenesis. 5 In rats, both adult and prenatal stress reduce learning performance, 6 suggesting, among other possibilities, parallel stress-induced changes in alternative splicing.…”

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confidence: 99%

SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA

et al. 2005

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“…But with increased age and slowed tissue regeneration, alternative splicing becomes more common also for the skin. In addition, this variation among different tissues could also be related to tissue‐specific modification of expression levels of transcription factors and splicing factors that could have either a direct or indirect effect on pre‐mRNA splicing (Meshorer & Soreq, 2002). …”

Section: Discussionmentioning

confidence: 99%

“…Previously thought to be a relatively uncommon phenomenon, AS has recently been shown to be widespread throughout the genome (Modrek & Lee, 2002). Studies in rats and mice have shown that increased age is associated with changes in mRNA processing leading to aberrant splicing (Yannarell et al ., 1977; Meshorer & Soreq, 2002). Normal aging has also been found to be associated with an aberrant increase in the production and maturation of many mRNAs in human peripheral blood leukocytes (Harries et al ., 2011).…”

Section: Introductionmentioning

confidence: 99%

Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

et al. 2015

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SummaryAlternative splicing (AS) is a key regulatory mechanism for the development of different tissues; however, not much is known about changes to alternative splicing during aging. Splicing events may become more frequent and widespread genome‐wide as tissues age and the splicing machinery stringency decreases. Using skin, skeletal muscle, bone, thymus, and white adipose tissue from wild‐type C57BL6/J male mice (4 and 18 months old), we examined the effect of age on splicing by AS analysis of the differential exon usage of the genome. The results identified a considerable number of AS genes in skeletal muscle, thymus, bone, and white adipose tissue between the different age groups (ranging from 27 to 246 AS genes corresponding to 0.3–3.2% of the total number of genes analyzed). For skin, skeletal muscle, and bone, we included a later age group (28 months old) that showed that the number of alternatively spliced genes increased with age in all three tissues (P < 0.01). Analysis of alternatively spliced genes across all tissues by gene ontology and pathway analysis identified 158 genes involved in RNA processing. Additional analysis of AS in a mouse model for the premature aging disease Hutchinson–Gilford progeria syndrome was performed. The results show that expression of the mutant protein, progerin, is associated with an impaired developmental splicing. As progerin accumulates, the number of genes with AS increases compared to in wild‐type skin. Our results indicate the existence of a mechanism for increased AS during aging in several tissues, emphasizing that AS has a more important role in the aging process than previously known.

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“…Many of the changes described in the literature report post-translational modifications, e. g., the advanced glycation endproducts (AGEs) which have been implicated in age-related disease and aging itself; as well as the p53 acetylation in stress-induced senescence (Furukawa et al, 2007). In addition, a growing body of evidence supports the involvement of the post-transcriptional modifications that occur in senescence, i. e., the alternative splicing processes associated with senescence (Harries et al, 2011;Meshorer & Soreq, 2002). Thus, alterations in the splicing pattern have been described for several age-related diseases, such as the Hutchison Gilford progeria syndrome (Eriksson et al, 2003), or the Alzheimer's disease-related tauopathies .…”

Section: Induction Of S-endoglin and Its Role In Endothelial Senescencementioning

confidence: 99%

Alternative Splicing in Endothelial Senescence: Role of the TGF-β Co-Receptor Endoglin

Blanco¹,

Bernabéu²

2012

Senescence

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Pre‐mRNA splicing modulations in senescence

Abstract: SummaryAging and associated diseases involve multilevel changes in the complex phenomenon of alternative splicing. Here, we review the potential genomic and environmental origins of such changes and discuss the research implications of these findings.

Cited by 79 publications

References 46 publications

SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA

SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA

Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

Alternative Splicing in Endothelial Senescence: Role of the TGF-β Co-Receptor Endoglin

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