L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells

Yang, Nuo; Kazazian, Haig H.

doi:10.1038/nsmb1141

Cited by 366 publications

(322 citation statements)

References 54 publications

Supporting

Mentioning

310

Contrasting

Unclassified

Order By: Relevance

“…2C). This was surprising, because previous studies have suggested that Dicer-dependent siRNAs processed from long double-stranded RNA precursors are important for silencing of these elements (7,16,29). The Dicer Ϫ/Ϫ ES cells analyzed here maintain genomic DNA methylation at satellite repeats and long interspersed nuclear elements (SI Fig.…”

Section: Analysis Of Repeat-overlapping Novel Readsmentioning

confidence: 69%

RNA sequence analysis defines Dicer's role in mouse embryonic stem cells

Calabrese

Seila

Yeo

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

301

269

View full text Add to dashboard Cite

Short RNA expression was analyzed from Dicer -positive and Dicer -knockout mouse embroyonic stem (ES) cells, using high-throughput pyrosequencing. A correlation of miRNA quantification with sequencing frequency estimates that there are 110,000 miRNAs per ES cell, the majority of which can be accounted for by six distinct miRNA loci. Four of these miRNA loci or their human homologues have demonstrated roles in cell cycle regulation or oncogenesis, suggesting that a major function of the miRNA pathway in ES cells may be to shape their distinct cell cycle. Forty-six previously uncharacterized miRNAs were identified, most of which are expressed at low levels and are less conserved than the set of known miRNAs. Low-abundance short RNAs matching all classes of repetitive elements were present in cells lacking Dicer , although the production of some SINE- and simple repeat-associated short RNAs appeared to be Dicer-dependent. These and other Dicer-dependent sequences resembled miRNAs. At a depth of sequencing that approaches the total number of 5′ phosphorylated short RNAs per cell, miRNAs appeared to be Dicer's only substrate. The results presented suggest a model in which repeat-associated miRNAs serve as host defenses against repetitive elements, a function canonically ascribed to other classes of short RNA.

show abstract

Section: Analysis Of Repeat-overlapping Novel Readsmentioning

confidence: 69%

RNA sequence analysis defines Dicer's role in mouse embryonic stem cells

Calabrese

Seila

Yeo

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

301

269

View full text Add to dashboard Cite

show abstract

“…Then, how is TE expression activated in early preimplantation embryos? Several studies have suggested that endogenous siRNAs against TEs play an important role in TE silencing [33][34][35][36]. Despite that this endogenous siRNA silencing system is functional in zygotes [37], certain classes of TEs somehow find a way to escape this silencing system for their activation in zygotes.…”

Section: Tet3-mediated 5mc Oxidation Is Dispensable For Zygotic Gene mentioning

confidence: 99%

Transcriptional activation of transposable elements in mouse zygotes is independent of Tet3-mediated 5-methylcytosine oxidation

2012

View full text Add to dashboard Cite

The methylation state of the paternal genome is rapidly reprogrammed shortly after fertilization. Recent studies have revealed that loss of 5-methylcytosine (5mC) in zygotes correlates with appearance of 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). This process is mediated by Tet3 and the 5mC oxidation products generated in zygotes are gradually lost during preimplantation development through a replicationdependent dilution process. Despite these findings, the biological significance of Tet3-mediated oxidation of 5mC to 5hmC/5fC/5caC in zygotes is unknown. DNA methylation plays an important role in silencing gene expression including the repression of transposable elements (TEs). Given that the activation of TEs during preimplantation development correlates with loss of DNA methylation, it is believed that paternal DNA demethylation may have an important role in TE activation. Here we examined this hypothesis and found that Tet3-mediated 5mC oxidation does not have a significant contribution to TE activation. We show that the expression of LINE-1 (long interspersed nucleotide element 1) and ERVL (endogenous retroviruses class III) are activated from both paternal and maternal genomes in zygotes. Inhibition of 5mC oxidation by siRNA-mediated depletion of Tet3 affected neither TE activation, nor global transcription in zygotes. Thus, our study provides the first evidence demonstrating that activation of both TEs and global transcription in zygotes are independent of Tet3-mediated 5mC oxidation.

show abstract

“…In males, this results in pachytene arrest (Bourc'his and Bestor 2004). It is also evident that small RNAs play an important role in the suppression of L1 retrotransposition in the mammalian germline (Girard et al 2006;Watanabe et al 2006;Yang and Kazazian Jr. 2006;Kuramochi-Miyagawa et al 2008). Finally the APOBEC3 family of RNA editing proteins have been shown to inhibit L1 activity in human cells (Bogerd et al 2006;Chen et al 2006;Muckenfuss et al 2006;Richardson et al 2014).…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for regional control

et al. 2018

View full text Add to dashboard Cite

Approximately half the mammalian genome is composed of repetitive sequences, and accumulating evidence suggests that some may have an impact on genome function. Here, we characterized a large array class of repeats of long-interspersed elements (LINE-1). Although widely distributed in mammals, locations of such arrays are species specific. Using targeted deletion, we asked whether a 170-kb LINE-1 array located at a mouse imprinted domain might function as a modulator of local transcriptional control. The LINE-1 array is lamina associated in differentiated ES cells consistent with its AT-richness, and although imprinting occurs both proximally and distally to the array, active LINE-1 transcripts within the tract are biallelically expressed. Upon deletion of the array, no perturbation of imprinting was observed, and abnormal phenotypes were not detected in maternal or paternal heterozygous or homozygous mutant mice. The array does not shield nonimprinted genes in the vicinity from local imprinting control. Reduced neural expression of protein-coding genes observed upon paternal transmission of the deletion is likely due to the removal of a brain-specific enhancer embedded within the LINE array. Our findings suggest that presence of a 170-kb LINE-1 array reflects the tolerance of the site for repeat insertion rather than an important genomic function in normal development.

show abstract

L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells

Cited by 366 publications

References 54 publications

RNA sequence analysis defines Dicer's role in mouse embryonic stem cells

RNA sequence analysis defines Dicer's role in mouse embryonic stem cells

Transcriptional activation of transposable elements in mouse zygotes is independent of Tet3-mediated 5-methylcytosine oxidation

Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for regional control

Contact Info

Product

Resources

About