Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation

Grant, Jennifer; Mahadevaiah, Shantha K.; Khil, Pavel P.; Sangrithi, Mahesh N.; Royo, Hélène; Duckworth, Janine A.; McCarrey, John R.; VandeBerg, John L.; Renfree, Marilyn B.; Taylor, Willie; Elgar, Greg; Camerini‐Otero, R. Daniel; Gilchrist, Michael J.; Turner, James M. A.

doi:10.1038/nature11171

Cited by 144 publications

(190 citation statements)

References 43 publications

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“…In support of this view, recent evidence has demonstrated a remarkable example of convergent evolution whereby eutherian (placental) and metatherian (marsupial) mammals independently evolved a ncRNA, Xist and Rsx, respectively, to regulate dosage compensation (inactivation) of the X chromosome (Duret et al 2006;Grant et al 2012).…”

Section: Introductionmentioning

confidence: 89%

Noncoding RNA and Polycomb recruitment

Brockdorff

2013

RNA

264

217

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A plethora of noncoding (nc) RNAs has been revealed through the application of high-throughput analysis of the transcriptome, and this has led to an intensive search for possible biological functions attributable to these transcripts. A major category of functional ncRNAs that has emerged is for those that are implicated in coordinate gene silencing, either in cis or in trans. The archetype for this class is the well-studied long ncRNA Xist which functions in cis to bring about transcriptional silencing of an entire X chromosome in female mammals. An important step in X chromosome inactivation is the recruitment of the Polycomb repressive complex PRC2 that mediates histone H3 lysine 27 methylation, a hallmark of the inactive X chromosome, and recent studies have suggested that this occurs as a consequence of PRC2 interacting directly with Xist RNA. Accordingly, other ncRNAs have been linked to PRC2 targeting either in cis or in trans, and here also the mechanism has been proposed to involve direct interaction between PRC2 proteins and the different ncRNAs. In this review, I discuss the evidence for and against this hypothesis, in the process highlighting alternative models and discussing experiments that, in the future, will help to resolve existing discrepancies.

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Section: Introductionmentioning

confidence: 89%

Noncoding RNA and Polycomb recruitment

Brockdorff

2013

RNA

264

217

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“…Based on the partial sequence homology in the syntenic region, the Xist gene was suggested to have evolved from a protein-coding gene, PDZRN3 (LNX3), which is found in more ancestral classes of animals than in marsupials such as birds, snakes, and amphibians (Duret et al 2006). Although this may imply that X-inactivation in marsupials is regulated by a completely distinct mechanism from the Xist-dependent one seen in eutherians, the recent finding of Rsx RNA in the opossum has raised an interesting and exciting possibility that marsupials still employ a mechanism synonymous with Xist RNA-mediated silencing (Grant et al 2012). Rsx RNA encoded on an X chromosome is another spliced lncRNA as long as 27 kb in length with no sequence similar to Xist RNA and is expressed only in females and coats the inactive X chromosome to form an Xist-like cloud.…”

Section: X-linked Lncrnas That Coat An X Chromosomementioning

confidence: 96%

Species-specific differences in X chromosome inactivation in mammals

Sado

Sakaguchi

2013

Reproduction

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In female mammals, the dosage difference in X-linked genes between XX females and XY males is compensated for by inactivating one of the two X chromosomes during early development. Since the discovery of the X inactive-specific transcript (XIST) gene in humans and its subsequent isolation of the mouse homolog, Xist, in the early 1990s, the molecular basis of X chromosome inactivation (X-inactivation) has been more fully elucidated using genetically manipulated mouse embryos and embryonic stem cells. Studies on X-inactivation in other mammals, although limited when compared with those in the mice, have revealed that, while their inactive X chromosome shares many features with those in the mice, there are marked differences in not only some epigenetic modifications of the inactive X chromosome but also when and how X-inactivation is initiated during early embryonic development. Such differences raise the issue about what extent of the molecular basis of X-inactivation in the mice is commonly shared among others. Recognizing similarities and differences in X-inactivation among mammals may provide further insight into our understanding of not only the evolutionary but also the molecular aspects for the mechanism of X-inactivation. Here, we reviewed species-specific differences in X-inactivation and discussed what these differences may reveal.

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“…This finding led to speculation that LINEs in autosomal monoallelically expressed regions were acting as "way stations" to aid the spreading of heterochromatin via a mechanism similar to that hypothesized for Xist in X inactivation at the time (Lyon 1998). However, this idea has been recently thrown into doubt because it is now believed that marsupials, who have LINE-poor X Chromosomes, also use a noncoding RNA (Rsx) to achieve XCI (Grant et al 2012). In mice, the Dlk1-Dio3 domain extends from Begain through to Dio3 (Fig.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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.

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Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation

Cited by 144 publications

References 43 publications

Noncoding RNA and Polycomb recruitment

Noncoding RNA and Polycomb recruitment

Species-specific differences in X chromosome inactivation in mammals

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

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