Evolutionary dynamics between transposable elements and their host genomes: mechanisms of suppression and escape DOI Creative Commons
Matthew A. Lawlor, Christopher E. Ellison

Current Opinion in Genetics & Development, Journal Year: 2023, Volume and Issue: 82, P. 102092 - 102092

Published: July 28, 2023

Transposable elements (TEs) are ubiquitous among eukaryotic species. Their evolutionary persistence is likely due to a combination of tolerogenic, evasive/antagonistic, and cooperative interactions with their host genomes. Here, we focus on metazoan species review recent advances related the harmful effects TE insertions, including how epigenetic TE-derived RNAs can damage cells. We discuss new findings pathways that silence TEs, such as piRNA pathway APOBEC3 Kruppel-associated box zinc finger gene families. Finally, summarize novel strategies used by TEs evade silencing, Y chromosome permissive niche for mobilization counterdefense block silencing factors.

Language: Английский

The lncRNA DUBR is regulated by CTCF and coordinates chromatin landscape and gene expression in hematopoietic cells DOI Creative Commons
Hober Nelson Núñez-Martínez, Gustavo Tapia-Urzúa, Ángel Josué Cerecedo-Castillo

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(4)

Published: Feb. 8, 2025

Abstract Master hematopoietic transcription factors (TFs) and long noncoding RNAs (lncRNAs) coordinate shaping lineage-specific gene expression programs during differentiation. The architectural protein CCCTC-binding factor (CTCF) has emerged as a pivotal regulator of in cell However, the relationship its regulatory effect CTCF on lncRNA genes hematopoiesis remain elusive. We demonstrated that constrains DUBRtranscription throughout erythroid DUBR is highly expressed human stem progenitor cells (HSPCs) but depleted erythroblasts. perturbation dysregulates hematopoietic-erythroid differentiation facilitates genome-wide activation elements. A genomic map RNA occupancy revealed associates with set involved regulating differentiation, including repressor HES1, which targets subset elements DUBR-dysregulated genes. Our results support role program by coordinating influencing their chromatin landscape.

Language: Английский

Citations

1
RNA stability controlled by m6A methylation contributes to X-to-autosome dosage compensation in mammals DOI Creative Commons
Cornelia Rücklé, Nadine Körtel, M. Felicia Basilicata

et al.

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(8), P. 1207 - 1215

Published: May 18, 2023

Abstract In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess X chromosome, while females (XX) undergo inactivation. To compensate for this reduction in dosage compared with two active copies of autosomes, it has been proposed that the chromosome exhibit compensation. However, existence and mechanisms X-to-autosome compensation still under debate. Here we show transcripts have fewer m 6 A modifications more stable than their autosomal counterparts. Acute depletion selectively stabilizes transcripts, resulting perturbed mouse embryonic stem cells. We propose higher stability is directed by lower levels A, indicating mammalian partly regulated epitranscriptomic RNA modifications.

Language: Английский

Citations

21
Age or lifestyle-induced accumulation of genotoxicity is associated with a length-dependent decrease in gene expression DOI Creative Commons
Olga Ibáñez-Solé, Irantzu Barrio, Ander Izeta

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(4), P. 106368 - 106368

Published: March 9, 2023

DNA damage has long been advocated as a molecular driver of aging. occurs in stochastic manner, and is therefore more likely to accumulate longer genes. The length-dependent accumulation transcription-blocking damage, unlike that somatic mutations, should be reflected gene expression datasets We analyzed function length several single-cell RNA sequencing mouse human found pervasive age-associated underexpression genes across species, tissues, cell types. Furthermore, we observed associated with UV-radiation smoke exposure, progeroid diseases, Cockayne syndrome, trichothiodystrophy. Finally, studied published sets showing global age-related changes. Genes underexpressed aging were significantly than overexpressed These data highlight previously undetected hallmark show genotoxicity could lead reduced polymerase II processivity.

Language: Английский

Citations

18
m 6 A RNA demethylase AtALKBH9B promotes mobilization of a heat-activated long terminal repeat retrotransposon in Arabidopsis DOI Creative Commons
W Fan, Ling Wang, Zhen Lei

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(48)

Published: Nov. 29, 2023

Transposons are mobile and ubiquitous DNA molecules that can cause vast genomic alterations. In plants, it is well documented transposon mobilization strongly repressed by methylation; however, its regulation at the posttranscriptional level remains relatively uninvestigated. Here, we suggest RNA marked m 6 A methylation be localized in stress granules (SGs). Intriguingly, SG-localized AtALKBH9B selectively demethylates a heat-activated retroelement, Onsen , thereby releases from spatial confinement, allowing for mobilization. addition, show evidence contributes to transpositional suppression inhibiting virus-like particle assembly extrachromosomal production. summary, this study unveils previously unknown role of mobility provides insight into how transposons counteract A-mediated repression mechanism hitchhiking demethylase host.

Language: Английский

Citations

17
RNA m6A modification, signals for degradation or stabilisation? DOI Creative Commons
Guifeng Wei

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(2), P. 707 - 717

Published: April 17, 2024

The RNA modification N6-methyladenosine (m6A) is conserved across eukaryotes, and profoundly influences metabolism, including regulating stability. METTL3 METTL14, together with several accessory components, form a ‘writer’ complex catalysing m6A modification. Conversely, FTO ALKBH5 function as demethylases, rendering dynamic. Key to understanding the functional significance of its ‘reader' proteins, exemplified by YTH-domain-containing proteins (YTHDFs) canonical reader insulin-like growth factor 2 mRNA-binding (IGF2BPs) non-canonical reader. These play crucial role in determining stability: YTHDFs mainly promote mRNA degradation through different cytoplasmic pathways, whereas IGF2BPs maintain Additionally, YTHDC1 functions within nucleus degrade or protect certain m6A-containing RNAs, other readers also contribute stability regulation. Notably, regulates retrotransposon LINE1 and/or transcription via multiple mechanisms. However, conflicting observations underscore complexities underlying m6A's regulation depending upon sequence/structure context, developmental stage, cellular environment. Understanding interplay between regulatory elements pivotal deciphering multifaceted roles plays broader biology.

Language: Английский

Citations

7
Context-specific effects of sequence elements on subcellular localization of linear and circular RNAs DOI Creative Commons
Maya Ron, Igor Ulitsky

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 5, 2022

Long RNAs vary extensively in their post-transcriptional fates, and this variation is attributed part to short sequence elements. We used massively parallel RNA assays study how sequences derived from noncoding influence the subcellular localization stability of circular linear RNAs, including spliced unspliced forms. find that effects elements strongly depend on host context, with limited overlap between drive nuclear enrichment RNAs. Binding specific binding proteins underpins some these differences-SRSF1 leads RNAs; SAFB associated predominantly IGF2BP1 promotes export molecules. The fate long thus dictated by combinatorial contributions elements, splicing, presence terminal features unique

Language: Английский

Citations

27
The RNA m6A landscape of mouse oocytes and preimplantation embryos DOI
Yunhao Wang, Yanjiao Li, Trine Skuland

et al.

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(5), P. 703 - 709

Published: April 20, 2023

Language: Английский

Citations

15
RNA m6A modification regulates L1 retrotransposons in human spermatogonial stem cell differentiation in vitro and in vivo DOI Creative Commons
Zili Li, Fang Fang, Mohammad Ishraq Zafar

et al.

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

Published: Feb. 16, 2024

Abstract The maintenance of genome integrity in the germline is crucial for mammalian development. Long interspersed element type 1 (LINE-1, L1) a mobile genetic that makes up about 17% human and poses threat to integrity. N6-methyl-adenosine (m 6 A) plays an essential role regulating various biological processes. However, function m A modification L1 retrotransposons development remains largely unknown. Here we knocked out methyltransferase METTL3 or reader YTHDF2 embryonic stem cells (hESCs) discovered are inducing spermatogonial (hSSCs) from hESCs vitro. removal resulted increased retrotransposition reduced efficiency SSC differentiation Further analysis showed recognizes METTL3-catalyzed degrades mRNA through autophagy, thereby blocking retrotransposition. Moreover, study confirmed fetal germ promotes degradation retrotransposon RNA, preventing insertion new into genome. Interestingly, RNA was highly expressed while significantly downregulated seminal plasma azoospermic patients with meiotic arrest compared males normal fertility. Additionally, identified some potentially pathogenic variants A-related genes men arrest. In summary, our suggests serves as guardian stability during provides novel insights regulatory mechanisms restricting

Language: Английский

Citations

6
SAFB restricts contact domain boundaries associated with L1 chimeric transcription DOI
Yaqiang Hong,

Luyao Bie,

Tao Zhang

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(9), P. 1637 - 1650.e10

Published: April 10, 2024

Language: Английский

Citations

5
Skipper analysis of eCLIP datasets enables sensitive detection of constrained translation factor binding sites DOI Creative Commons
Evan A. Boyle, Hsuan-Lin Her, Jasmine R. Mueller

et al.

Cell Genomics, Journal Year: 2023, Volume and Issue: 3(6), P. 100317 - 100317

Published: May 4, 2023

Technology for crosslinking and immunoprecipitation (CLIP) followed by sequencing (CLIP-seq) has identified the transcriptomic targets of hundreds RNA-binding proteins in cells. To increase power existing future CLIP-seq datasets, we introduce Skipper, an end-to-end workflow that converts unprocessed reads into annotated binding sites using improved statistical framework. Compared with methods, Skipper on average calls 210%-320% more sometimes >1,000% sites, providing deeper insight post-transcriptional gene regulation. also to repetitive elements identifies bound 99% enhanced CLIP experiments. We perform nine translation factor CLIPs apply learn determinants occupancy, including transcript region, sequence, subcellular localization. Furthermore, observe depletion genetic variation occupied nominate transcripts subject selective constraint because occupancy. offers fast, easy, customizable, state-of-the-art analysis data.

Language: Английский

Citations

13