Novel conserved human DNA sequence supports expression of long genes DOI Open Access
Jay C. Brown

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 21, 2023

Abstract The study described here was carried out to pursue the idea that a truncated, transposition incompetent fragment of LINE1 retrotransposon may affect expression human gene when it is located inside sequence. NCBI BLAST used probe genome identify protein coding genes containing an abundant ∼1500bp (called t1519) in body. length and level such then compared with same properties lack t1519 chromosomes 16-18. results showed striking effect on long genes, those lengths greater than ∼140 kb. Nearly all were found have one or more sequences region. In contrast, common range (less 140 kb) could either not. A correlation also observed expression. While long, t1519-containing limited ∼50 TPM, be much higher, 500-600 regardless whether not they elements. Contrasting obtained analysis performed lncRNAs rather protein-coding genes. Among lncRNA chromosome-specific observed. Restricted correlating presence both 16 17, but chromosome 18. are interpreted support strong suppressive 17. It suggested expression, particularly among meets need for cell limit overall transcription can support. Author summary Although DNA sequence elements well known their ability replicate move autonomously within genome, these features only small proportion (0.02%) total population. ∼500,000 fragments full-length inactive autonomous replication movement. Truncated, throughout including body this intragenic population subject here. goal extend what about sequences. t1519, truncated composed 3’ terminal ∼1500 bp ∼6000 full element, three 16, 17 18, rich each chromosome, control lacking t1519. result case longer had body, introns. An Low (<50 TPM) positive while higher levels (500-600 (< Similar studied instead ones. certain due

Language: Английский

Transposon–host arms race: a saga of genome evolution DOI
Yuka W. Iwasaki, Keisuke Shoji,

Shinichi Nakagwa

et al.

Trends in Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

2
Regulation and function of transposable elements in cancer genomes DOI Creative Commons
Michael Lee, Syed Farhan Ahmad, Jian Xu

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: March 31, 2024

Abstract Over half of human genomic DNA is composed repetitive sequences generated throughout evolution by prolific mobile genetic parasites called transposable elements (TEs). Long disregarded as “junk” or “selfish” DNA, TEs are increasingly recognized formative in genome evolution, wired intimately into the structure and function genome. Advances sequencing technologies computational methods have ushered an era unprecedented insight how TE activity impacts biology health disease. Here we discuss current views on shaped regulatory landscape genome, implicated cancers, recent findings motivate novel strategies to leverage for improved cancer therapy. Given crucial role methodological advances biology, pair our conceptual discussions with in-depth review inherent technical challenges studying repeats, specifically related structural variation, expression analyses, chromatin regulation. Lastly, provide a catalog existing emerging assays bioinformatic software that altogether enabling most sophisticated comprehensive investigations yet regulation interspersed repeats genomes.

Language: Английский

Citations

6
Transposon exonization generates new protein-coding sequences DOI

Yantao Hong,

Xiaohua Shen

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(1), P. 7 - 8

Published: Jan. 1, 2025

Language: Английский

Citations

0
An RNA Splicing System that Excises Transposons from Animal mRNAs DOI Creative Commons

Long‐Wen Zhao,

Christopher Nardone, João A. Paulo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract All genomes harbor mobile genetic parasites called transposable elements (TEs). Here we describe a system, which term SOS splicing, that protects C. elegans and human genes from DNA transposon-mediated disruption by excising these TEs host mRNAs. operates independently of the spliceosome, is pattern recognition system triggered base-pairing inverted terminal repeat elements, are defining feature transposons. We identify three factors required for splicing in both cells; AKAP17A, binds TE-containing mRNAs; RNA ligase RTCB; CAAP1, bridges RTCB allowing to ligate mRNA fragments generated TE excision. propose novel, conserved, structure-directed mode one function genetically buffer animals deleterious effects TE-mediated gene perturbation.

Language: Английский

Citations

0
Intermittent fasting attenuates CNS inflammaging - rebalancing the transposonome DOI Creative Commons
Mitchell J Cummins, Ethan T Cresswell, Doug W. Smith

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract A hallmark of CNS aging is sterile, chronic, low-grade neuroinflammation. Understanding how the develops chronic inflammation necessary to achieve extended healthspan. Characterisation neuroinflammatory molecular triggers remains limited. Interventions that reduce neuroinflammation and extend health lifespan could be useful in this regard. One such intervention intermittent fasting (IF), but IF impacts insufficiently understood. To address this, we performed deep RNA-sequencing on young, middle-aged, old, mouse regions. Additionally, sequenced spinal cord animals subject adult lifelong IF. We found most differentially expressed genes (DEGs) at middle age were region specific (~ 50–84%), whilst effect weakened 18–72%) old age, suggesting emergence a more general global profile. DEGs from all regions enriched for inflammatory immune ontologies. Surprisingly, SC was aging- neuroinflammation-impacted both ages, with by far highest number DEGs, largest net increase expression transposable elements (TEs), greatest enrichment immune-related ontologies, generally larger increases gene expression. Overall, normal upregulation sensors non-self, DNA/RNA, activation inflammasomes, cGAS-STING1 interferon response genes, across CNS. Whilst still developed an profile SC, average lower ~ 50% compared age-matched controls. IF-specific apparent, also acts separate, potentially targetable, pathways those impacted aging. Expression disease associated microglia, phagocytic exhaustion, STING1, inflammasome decreased Significantly, TE reversed decrease. In summary, find hotspot, attenuates neuroinflammaging rebalancing transposonome.

Language: Английский

Citations

0
Selective identification of epigenetic regulators at methylated genomic sites by SelectID DOI Creative Commons
Wenchang Qian, Penglei Jiang, Mingming Niu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 18, 2025

DNA methylation is a significant component in proximal chromatin regulation and plays crucial roles regulating gene expression maintaining the repressive state of retrotransposon elements. However, accurate profiling proteomics which simultaneously identifies specific sequences their associated epigenetic modifications remains challenge. Here, we report strategy termed SelectID (selective control at genome targets identified by dCas9), introduces methylated binding domain into dCas9-mediated proximity labeling system to enable situ protein capture repetitive elements with 5-methylcytosine (5mC) modifications. demonstrated as feasible dCas9-TurboID regions, such chromosome 9 satellite. Using SelectID, successfully identify CHD4 potential repressors long interspersed nuclear element-1 (LINE-1) through direct 5' untranslated region (5'UTR) young LINE-1 Overall, our approach has opened up avenues for uncovering regulators regions methylation, will greatly facilitate future studies on regulation.

Language: Английский

Citations

0
Biomolecular liquid‒liquid phase separation associated with repetitive genomic elements DOI
Sefan Asamitsu, Yuka W. Iwasaki

Polymer Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Language: Английский

Citations

0
Transposable elements as instructors of the immune system DOI
Lisa Schmidleithner, Philipp Stüve, Markus Feuerer

et al.

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Language: Английский

Citations

0
From computational models of the splicing code to regulatory mechanisms and therapeutic implications DOI
Charlotte Capitanchik, Oscar G. Wilkins, Nils Wagner

et al.

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 2, 2024

Language: Английский

Citations

2
Retrotransposon life cycle and its impacts on cellular responses DOI Creative Commons
Ahmad Luqman-Fatah,

Kei Nishimori,

Shota Amano

et al.

RNA Biology, Journal Year: 2024, Volume and Issue: 21(1), P. 11 - 27

Published: Oct. 13, 2024

Approximately 45% of the human genome is comprised transposable elements (TEs), also known as mobile genetic elements. However, their biological function remains largely unknown. Among them, retrotransposons are particularly abundant, and some copies still capable mobilization within through RNA intermediates. This review focuses on life cycle summarizes regulatory mechanisms impacts cellular processes. Retrotransposons generally epigenetically silenced in somatic cells, but transcriptionally reactivated under certain conditions, such tumorigenesis, development, stress, ageing, potentially leading to instability. We explored dual nature genomic parasites elements, focusing roles diversity innate immunity. Furthermore, we discuss how host factors regulate retrotransposon cDNA intermediates binding, modification, degradation. The interplay between machinery provides insight into complex regulation potential for dysregulation cause aberrant responses inflammation autoimmune diseases.

Language: Английский

Citations

2