Similar Datasets
Project description:Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-mRNA synthesis, intronic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product as they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns (Huff et al. 2016), and functional (Cosby et al. 2021) or non-functional chimeric transcripts (Clayton et al. 2020). The rarity of these events impliesy the existence of a resilient splicing code that is able to suppress TE-exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins play a unique dual role in defence against TEs by preventing retrotransposition of L1 elements as well as their exonization when they land into genes by coating their adenosine-rich RNA. The suppressive activity of SAFB extends to neuro-, muscle- and testis-specific giant protein-coding cassette exons of ANK3, MAP4 and CLIP1, nested genes as well as Tigger DNA transposons, which are all enriched with adenosine/purine-rich sequences that act as splicing-enhancers in SAFB depleted cells. In mice and flies, SAFB additionally suppresses LTR/ERV elements, which are active in mice and flies, but no longer in humans. Splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in post-meiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-piRNA pathway of the germline.
2024-01-08 | GSE244699 | GEO
Project description:Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-mRNA synthesis, intronŁic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product as they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns (Huff et al. 2016), and functional (Cosby et al. 2021) or non-functional chimeric transcripts (Clayton et al. 2020). The rarity of these events impliesy the existence of a resilient splicing code that is able to suppress TE-exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins play a unique dual role in defence against TEs by preventing retrotransposition of L1 elements as well as their exonization when they land into genes by coating their adenosine-rich RNA. The suppressive activity of SAFB extends to neuro-, muscle- and testis-specific giant protein-coding cassette exons of ANK3, MAP4 and CLIP1, nested genes as well as Tigger DNA transposons, which are all enriched with adenosine/purine-rich sequences that act as splicing-enhancers in SAFB depleted cells. In mice and flies, SAFB additionally suppresses LTR/ERV elements, which are active in mice and flies, but no longer in humans. Splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in post-meiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-piRNA pathway of the germline.
2024-01-08 | GSE223262 | GEO
Project description:Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-mRNA synthesis, intronŁic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product as they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns (Huff et al. 2016), and functional (Cosby et al. 2021) or non-functional chimeric transcripts (Clayton et al. 2020). The rarity of these events impliesy the existence of a resilient splicing code that is able to suppress TE-exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins play a unique dual role in defence against TEs by preventing retrotransposition of L1 elements as well as their exonization when they land into genes by coating their adenosine-rich RNA. The suppressive activity of SAFB extends to neuro-, muscle- and testis-specific giant protein-coding cassette exons of ANK3, MAP4 and CLIP1, nested genes as well as Tigger DNA transposons, which are all enriched with adenosine/purine-rich sequences that act as splicing-enhancers in SAFB depleted cells. In mice and flies, SAFB additionally suppresses LTR/ERV elements, which are active in mice and flies, but no longer in humans. Splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in post-meiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-piRNA pathway of the germline.
2024-01-08 | GSE223261 | GEO
Project description:Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-mRNA synthesis, intronic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product as they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns (Huff et al. 2016), and functional (Cosby et al. 2021) or non-functional chimeric transcripts (Clayton et al. 2020). The rarity of these events impliesy the existence of a resilient splicing code that is able to suppress TE-exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins play a unique dual role in defence against TEs by preventing retrotransposition of L1 elements as well as their exonization when they land into genes by coating their adenosine-rich RNA. The suppressive activity of SAFB extends to neuro-, muscle- and testis-specific giant protein-coding cassette exons of ANK3, MAP4 and CLIP1, nested genes as well as Tigger DNA transposons, which are all enriched with adenosine/purine-rich sequences that act as splicing-enhancers in SAFB depleted cells. In mice and flies, SAFB additionally suppresses LTR/ERV elements, which are active in mice and flies, but no longer in humans. Splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in post-meiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-piRNA pathway of the germline.
2024-01-08 | GSE223257 | GEO
Project description:Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-mRNA synthesis, intronic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product as they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns (Huff et al. 2016), and functional (Cosby et al. 2021) or non-functional chimeric transcripts (Clayton et al. 2020). The rarity of these events impliesy the existence of a resilient splicing code that is able to suppress TE-exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins play a unique dual role in defence against TEs by preventing retrotransposition of L1 elements as well as their exonization when they land into genes by coating their adenosine-rich RNA. The suppressive activity of SAFB extends to neuro-, muscle- and testis-specific giant protein-coding cassette exons of ANK3, MAP4 and CLIP1, nested genes as well as Tigger DNA transposons, which are all enriched with adenosine/purine-rich sequences that act as splicing-enhancers in SAFB depleted cells. In mice and flies, SAFB additionally suppresses LTR/ERV elements, which are active in mice and flies, but no longer in humans. Splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in post-meiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-piRNA pathway of the germline.
2024-01-08 | GSE244711 | GEO
Project description:Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-mRNA synthesis, intronŁic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product as they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns (Huff et al. 2016), and functional (Cosby et al. 2021) or non-functional chimeric transcripts (Clayton et al. 2020). The rarity of these events impliesy the existence of a resilient splicing code that is able to suppress TE-exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins play a unique dual role in defence against TEs by preventing retrotransposition of L1 elements as well as their exonization when they land into genes by coating their adenosine-rich RNA. The suppressive activity of SAFB extends to neuro-, muscle- and testis-specific giant protein-coding cassette exons of ANK3, MAP4 and CLIP1, nested genes as well as Tigger DNA transposons, which are all enriched with adenosine/purine-rich sequences that act as splicing-enhancers in SAFB depleted cells. In mice and flies, SAFB additionally suppresses LTR/ERV elements, which are active in mice and flies, but no longer in humans. Splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in post-meiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-piRNA pathway of the germline.
2024-01-08 | GSE244708 | GEO
Project description:Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-mRNA synthesis, intronŁic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product as they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns (Huff et al. 2016), and functional (Cosby et al. 2021) or non-functional chimeric transcripts (Clayton et al. 2020). The rarity of these events impliesy the existence of a resilient splicing code that is able to suppress TE-exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins play a unique dual role in defence against TEs by preventing retrotransposition of L1 elements as well as their exonization when they land into genes by coating their adenosine-rich RNA. The suppressive activity of SAFB extends to neuro-, muscle- and testis-specific giant protein-coding cassette exons of ANK3, MAP4 and CLIP1, nested genes as well as Tigger DNA transposons, which are all enriched with adenosine/purine-rich sequences that act as splicing-enhancers in SAFB depleted cells. In mice and flies, SAFB additionally suppresses LTR/ERV elements, which are active in mice and flies, but no longer in humans. Splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in post-meiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-piRNA pathway of the germline.
2024-01-08 | GSE244701 | GEO
Project description:Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-mRNA synthesis, intronŁic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product as they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns (Huff et al. 2016), and functional (Cosby et al. 2021) or non-functional chimeric transcripts (Clayton et al. 2020). The rarity of these events impliesy the existence of a resilient splicing code that is able to suppress TE-exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins play a unique dual role in defence against TEs by preventing retrotransposition of L1 elements as well as their exonization when they land into genes by coating their adenosine-rich RNA. The suppressive activity of SAFB extends to neuro-, muscle- and testis-specific giant protein-coding cassette exons of ANK3, MAP4 and CLIP1, nested genes as well as Tigger DNA transposons, which are all enriched with adenosine/purine-rich sequences that act as splicing-enhancers in SAFB depleted cells. In mice and flies, SAFB additionally suppresses LTR/ERV elements, which are active in mice and flies, but no longer in humans. Splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in post-meiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-piRNA pathway of the germline.
2024-01-08 | GSE223254 | GEO
Project description:Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-mRNA synthesis, intronic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product as they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns (Huff et al. 2016), and functional (Cosby et al. 2021) or non-functional chimeric transcripts (Clayton et al. 2020). The rarity of these events impliesy the existence of a resilient splicing code that is able to suppress TE-exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins play a unique dual role in defence against TEs by preventing retrotransposition of L1 elements as well as their exonization when they land into genes by coating their adenosine-rich RNA. The suppressive activity of SAFB extends to neuro-, muscle- and testis-specific giant protein-coding cassette exons of ANK3, MAP4 and CLIP1, nested genes as well as Tigger DNA transposons, which are all enriched with adenosine/purine-rich sequences that act as splicing-enhancers in SAFB depleted cells. In mice and flies, SAFB additionally suppresses LTR/ERV elements, which are active in mice and flies, but no longer in humans. Splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in post-meiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-piRNA pathway of the germline.
2024-01-08 | GSE223253 | GEO
Project description:Programmed cell death pathways eliminate infected cells and regulate infection-associated inflammation during pathogen invasion. Cytomegaloviruses encode several distinct suppressors that block intrinsic apoptosis, extrinsic apoptosis, and necroptosis, pathways that impact pathogenesis of this ubiquitous herpesvirus. Here, we expanded the understanding of three cell autonomous suppression mechanisms on which murine cytomegalovirus relies: (i) M38.5-encoded viral mitochondrial inhibitor of apoptosis (vMIA), a BAX suppressor that functions in concert with M41.1-encoded viral inhibitor of BAK oligomerization (vIBO), (ii) M36-encoded viral inhibitor of caspase-8 activation (vICA), and (iii) M45-encoded viral inhibitor of RIP/RHIM activation (vIRA). Following infection of bone marrow-derived macrophages, the virus initially deflected receptor-interacting protein kinase (RIPK)3-dependent necroptosis, the most potent of the three cell death pathways. This process remained independent of caspase-8, although suppression of this apoptotic protease enhances necroptosis in most cell types. Second, the virus deflected TNF-mediated extrinsic apoptosis, a pathway dependent on autocrine TNF production by macrophages that proceeds independently of mitochondrial death machinery or RIPK3. Third, cytomegalovirus deflected BCL-2 family protein-dependent mitochondrial cell death through combined TNF-dependent and -independent signaling even in the absence of RIPK1, RIPK3, and caspase-8. Furthermore, each of these cell death pathways dictated a distinct pattern of cytokine and chemokine activation. Therefore, cytomegalovirus employs sequential, non-redundant suppression strategies to specifically modulate the timing and execution of necroptosis, extrinsic apoptosis, and intrinsic apoptosis within infected cells to orchestrate virus control and infection-dependent inflammation. Virus-encoded death suppressors together hold control over an intricate network that upends host defense and supports pathogenesis in the intact mammalian host.
| S-EPMC8473406 | biostudies-literature