TEspeX: consensus-specific quantification of transposable element expression preventing biases from exonized fragments

Ansaloni, Federico; Gualandi, Nicolò; Esposito, Mauro; Gustincich, Stefano; Sanges, Remo

doi:10.1093/bioinformatics/btac526

Cited by 9 publications

(15 citation statements)

References 31 publications

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“…In order to verify this hypothesis, we selected the 799 upregulated extragenic L1s to represent the group of potentially autonomously transcribed L1 elements (referred to as active L1s). This set was chosen since they should less likely be involved in passive transcription as part of canonical transcripts [ 54 ], therefore reducing possible background noise from exonized L1s. We then identified the miRNA target sites both in the active L1s and in the 3′UTRs of protein-coding genes.…”

Section: Resultsmentioning

confidence: 99%

“…The aim of our analyses was to validate the activity of L1 as a ceRNA exploiting a cellular context perturbed exclusively by the overexpression of a single L1 without affecting DNA methylation. To assess the capability of ORFeus-OE model to overexpress the artificial L1 construct, we used the consensus-specific tool TEspeX [ 54 ], quantifying TE transcription levels. From the differential expression analysis, seven TE subfamilies were upregulated and two downregulated.…”

Section: Resultsmentioning

confidence: 99%

“…In order to investigate the TE transcriptome of the ORFeus-OE model, we used the TEspeX [ 54 ] software. For the analysis, we provided a modified version of TE consensus sequences from the Dfam database [ 55 ] that includes the L1-ORFeus sequence ( accessed on 24 August 2021).…”

Section: Methodsmentioning

confidence: 99%

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Transposons Acting as Competitive Endogenous RNAs: In-Silico Evidence from Datasets Characterised by L1 Overexpression

et al. 2022

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LINE L1 are transposable elements that can replicate within the genome by passing through RNA intermediates. The vast majority of these element copies in the human genome are inactive and just between 100 and 150 copies are still able to mobilize. During evolution, they could have been positively selected for beneficial cellular functions. Nonetheless, L1 deregulation can be detrimental to the cell, causing diseases such as cancer. The activity of miRNAs represents a fundamental mechanism for controlling transcript levels in somatic cells. These are a class of small non-coding RNAs that cause degradation or translational inhibition of their target transcripts. Beyond this, competitive endogenous RNAs (ceRNAs), mostly made by circular and non-coding RNAs, have been seen to compete for the binding of the same set of miRNAs targeting protein coding genes. In this study, we have investigated whether autonomously transcribed L1s may act as ceRNAs by analyzing public dataset in-silico. We observed that genes sharing miRNA target sites with L1 have a tendency to be upregulated when L1 are overexpressed, suggesting the possibility that L1 might act as ceRNAs. This finding will help in the interpretation of transcriptomic responses in contexts characterized by the specific activation of transposons.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Transposons Acting as Competitive Endogenous RNAs: In-Silico Evidence from Datasets Characterised by L1 Overexpression

et al. 2022

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“…To quantify L1 expression two software were used: TEspeX (45) and SQuIRE (47). TEspeX measures TE expression not counting reads possibly generated from TE fragments embedded in the exons of annotated transcripts, and cumulatively quanti es the expression of TE subfamilies annotated in RepeatMasker(29) by counting the sequencing reads mapped to the consensus sequence of each TE subfamily.…”

Section: Resultsmentioning

confidence: 99%

“…The number of reads mapping to each genomic feature de ned as 'exon' in the GTF le retrieved from gencode version v32lift37 were quanti ed. In order to quantify TEs expression, we used two different software: and TEspeX (45). The two tools employ distinct strategies to assess TEs transcriptional activity.…”

Section: Tes and Gene Quanti Cation And Differential Expressionmentioning

confidence: 99%

Exploratory Analysis of L1 retrotransposons expression in Autism

Spirito

Filosi

Domenici

et al. 2022

Preprint

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Background Autism Spectrum Disorder (ASD) is a set of highly heterogeneous neurodevelopmental diseases whose genetic etiology is not completely understood. Several investigations have relied on transcriptome analysis from peripheral tissues to dissect ASD into homogenous molecular phenotypes. Recently, alterations of gene expression from post-mortem brain tissues have identified sets of genes with altered expression, mapping on pathways known to be involved in ASD etiology. In addition to protein-coding transcripts, the human transcriptome is composed by a large set of non-coding RNAs and transposable elements (TEs). Advancements in sequencing technologies have proved that TEs can be transcribed in a regulated fashion, and their dysregulation have a role in neural diseases. Methods We exploited published datasets comprising RNA-seq data from 1) post-mortem brain of ASD subjects, 2) in vitro cell cultures where ten different ASD-relevant genes were knocked out and 3) blood of discordant siblings. We measured the expression levels of evolutionarily young full-length transposable L1 elements and characterized the genomic location of deregulated L1s assessing their potential impact on the transcription of ASD-relevant genes. Results We detected a strong upregulation of intronic full length L1s exclusively in a subset of samples where the number of deregulated genes correlates with L1 upregulation. In brain tissue, specific upregulated L1s overlap ASD-relevant downregulated genes, suggesting the existence of a negative effect of L1 transcription on host transcripts for a subset of ASD genes. Limitations Our analyses are limited by the low number of samples and by the lack of replicates among post-mortem brain samples. Measuring the transcription of locus-specific TEs is complicated by the repetitive nature of their sequence, which reduces the accuracy in mapping sequencing reads to the correct genomic locus. Conclusions We observed L1s upregulation in a subset of ASD samples. In these cases, L1 upregulation might directly impair the expression of ASD-relevant genes by a mechanism not yet understood. L1s upregulation in autism appears to be limited to a subset of subjects probably harbouring mutations in genes related to DNA/chromatin modification.

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Transcription of endogenous retroviruses in senescent cells contributes to the accumulation of double-stranded RNAs that trigger an anti-viral response that reinforces senescence

Di Giorgio,

Ranzino,

Tolotto

et al. 2024

Cell Death Dis

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An important epigenetic switch marks the onset and maintenance of senescence. This allows transcription of the genetic programs that arrest the cell cycle and alter the microenvironment. Transcription of endogenous retroviruses (ERVs) is also a consequence of this epigenetic switch. In this manuscript, we have identified a group of ERVs that are epigenetically silenced in proliferating cells but are upregulated during replicative senescence or during various forms of oncogene-induced senescence, by RAS and Akt, or after HDAC4 depletion. In a HDAC4 model of senescence, removal of the repressive histone mark H3K27me3 is the plausible mechanism that allows the transcription of intergenic ERVs during senescence. We have shown that ERVs contribute to the accumulation of dsRNAs in senescence, which can initiate the antiviral response via the IFIH1-MAVS signaling pathway and thus contribute to the maintenance of senescence. This pathway, and MAVS in particular, plays an active role in shaping the microenvironment and maintaining growth arrest, two essential features of the senescence program.

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TEspeX: consensus-specific quantification of transposable element expression preventing biases from exonized fragments

Cited by 9 publications

References 31 publications

Transposons Acting as Competitive Endogenous RNAs: In-Silico Evidence from Datasets Characterised by L1 Overexpression

Transposons Acting as Competitive Endogenous RNAs: In-Silico Evidence from Datasets Characterised by L1 Overexpression

Exploratory Analysis of L1 retrotransposons expression in Autism

Transcription of endogenous retroviruses in senescent cells contributes to the accumulation of double-stranded RNAs that trigger an anti-viral response that reinforces senescence

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