An Alu-derived intronic splicing enhancer facilitates intronic processing and modulates aberrant splicing in ATM

Pastor, Tibor J.; Talotti, Gabriele; Lewandowska, Marzena Anna; Pagani, Franco

doi:10.1093/nar/gkp778

Cited by 22 publications

(23 citation statements)

References 57 publications

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“…The inclusion of exon 20A was associated with a deletion of four nucleotides (GTAA) in intron 20. The authors identified a novel regulatory element within intron 20, termed “intron-splicing processing element” (ISPE), which acts as an intronic silencer of a cryptic 3′ splice site [93–95]. The ISPE is recognized by the U1 snRNP, a core component of the splicing apparatus that normally binds the 5′ splice site.…”

Section: How As Can Affect the Ddrmentioning

confidence: 99%

RNA Splicing: A New Player in the DNA Damage Response

Lenzken

Loffreda

Barabino

2013

International Journal of Cell Biology

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It is widely accepted that tumorigenesis is a multistep process characterized by the sequential accumulation of genetic alterations. However, the molecular basis of genomic instability in cancer is still partially understood. The observation that hereditary cancers are often characterized by mutations in DNA repair and checkpoint genes suggests that accumulation of DNA damage is a major contributor to the oncogenic transformation. It is therefore of great interest to identify all the cellular pathways that contribute to the response to DNA damage. Recently, RNA processing has emerged as a novel pathway that may contribute to the maintenance of genome stability. In this review, we illustrate several different mechanisms through which pre-mRNA splicing and genomic stability can influence each other. We specifically focus on the role of splicing factors in the DNA damage response and describe how, in turn, activation of the DDR can influence the activity of splicing factors.

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Section: How As Can Affect the Ddrmentioning

confidence: 99%

RNA Splicing: A New Player in the DNA Damage Response

Lenzken

Loffreda

Barabino

2013

International Journal of Cell Biology

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“…Splicing enhancers and silencers are 10-nucleotide-long ncRNAs that interact with SR proteins and snRNAs. They are formed by processing transcripts of Alu retroelements (Pastor et al, 2009). TEs turned out to be sources of satellites due to the capability of site-specific insertions (McGurk, Barbash, 2018) and illegitimate recombination, followed by amplification by gene conversion (Han et al, 2016).…”

Section: Other Functions Of Transposable Elementsmentioning

confidence: 99%

Involvement of transposable elements in neurogenesis

Мустафин

Хуснутдинова

2020

Vestn. VOGiS

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The article is about the role of transposons in the regulation of functioning of neuronal stem cells and mature neurons of the human brain. Starting from the first division of the zygote, embryonic development is governed by regular activations of transposable elements, which are necessary for the sequential regulation of the expression of genes specific for each cell type. These processes include differentiation of neuronal stem cells, which requires the finest tuning of expression of neuron genes in various regions of the brain. Therefore, in the hippocampus, the center of human neurogenesis, the highest transposon activity has been identified, which causes somatic mosai cism of cells during the formation of specific brain structures. Similar data were obtained in studies on experimental animals. Mobile genetic elements are the most important sources of long non-coding RNAs that are coexpressed with important brain protein-coding genes. Significant activity of long non-coding RNA was detected in the hippocampus, which confirms the role of transposons in the regulation of brain function. MicroRNAs, many of which arise from transposon transcripts, also play an important role in regulating the differentiation of neuronal stem cells. Therefore, transposons, through their own processed transcripts, take an active part in the epigenetic regulation of differentiation of neurons. The global regulatory role of transposons in the human brain is due to the emergence of protein-coding genes in evolution by their exonization, duplication and domestication. These genes are involved in an epigenetic regulatory network with the participation of transposons, since they contain nucleotide sequences complementary to miRNA and long non-coding RNA formed from transposons. In the memory formation, the role of the exchange of virus-like mRNA with the help of the Arc protein of endogenous retroviruses HERV between neurons has been revealed. A possible mechanism for the implementation of this mechanism may be reverse transcription of mRNA and site-specific insertion into the genome with a regulatory effect on the genes involved in the memory.

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“…[40][41][42] Alu insertion/deletion polymorphism has been reported to be in total linkage disequilibrium with CTG repeats in myotonic dystrophy. 43 Several reports [44][45][46][47][48][49] indicate that de novo Alu insertions into intronic sequences in close proximity to the affected exon cause the downstream exon to shift from constitutive splicing to full exon skipping or alternative splicing (Table 2).…”

Section: Intronic Alterations Affect Splicing Of Capn3 Genementioning

confidence: 99%

CAPN3 mRNA processing alteration caused by splicing mutation associated with novel genomic rearrangement of Alu elements

et al. 2011

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Recessive mutations of CAPN3 gene are reported to be responsible for limb girdle muscular dystrophy type 2A (LGMD2A). In all, 15-25% of intronic nucleotide changes identified in this gene were investigated by in silico analysis, but occasionally supported by experimental data or reported in some cases as a polymorphism. We report here genetic and transcriptional analyses in three Tunisian patients belonging to the same consanguineous family sharing the same mutation c.1194-9 A4G and Alu repeats insertion in intron 7 of CAPN3 gene. Reverse transcriptase-PCR experiments performed on total RNA from the patient's muscle biopsy showed retention of the eight last nucleotides of intron 9 in the CAPN3 transcript lacking the first seven exons. Our results provide evidence regarding the potential involvement of Alu elements in aberrant processing of pre-mRNA owing to the disruption of pre-existing intronic splicing regulatory elements. We also demonstrated variable mRNA alternative splicing among tissues and between LGMD2A patients. A deep intronic variation and rearrangement have been reported in the literature as causing genetic diseases in humans. However, this is the first report on a potential pathogenic CAPN3 gene mutation resulting from an Alu insertion.

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An Alu-derived intronic splicing enhancer facilitates intronic processing and modulates aberrant splicing in ATM

Cited by 22 publications

References 57 publications

RNA Splicing: A New Player in the DNA Damage Response

RNA Splicing: A New Player in the DNA Damage Response

Involvement of transposable elements in neurogenesis

CAPN3 mRNA processing alteration caused by splicing mutation associated with novel genomic rearrangement of Alu elements

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