Chromosomal RNA: Its Properties

Holmes, David S.; Mayfield, John E.; Sander, Gernot; Bonner, James

doi:10.1126/science.177.4043.72

Cited by 81 publications

(41 citation statements)

References 17 publications

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“…A “nuclear matrix” consisting of insoluble proteins and RNA particles was proposed to organize interphase chromatin architecture (Berezney and Coffey, 1974, Pederson, 1998), maintain chromosome territories (Ma et al., 1999), enhance gene expression, and provide a platform for nuclear processes, but chromatin mobility in vivo (Chubb et al., 2002, Phair et al., 2004) and the lack of a stable nucleoprotein structure in live cells undermined the concept (Hancock, 2000). However, the structural contribution of RNA to chromatin organization remains undisputed: a large proportion of chromatin by mass corresponds to RNA (Holmes et al., 1972), mostly belonging to the loosely termed chromatin-associated RNA (caRNA) class. The functional roles of caRNAs are hinted by the observation that they are stably associated with interphase chromosome territories (Fey et al., 1986, Hall and Lawrence, 2016) and their disruption leads to chromatin condensation (Hall et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs

Nozawa

Boteva

Soares

et al. 2017

Cell

194

216

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SummaryHigher eukaryotic chromosomes are organized into topologically constrained functional domains; however, the molecular mechanisms required to sustain these complex interphase chromatin structures are unknown. A stable matrix underpinning nuclear organization was hypothesized, but the idea was abandoned as more dynamic models of chromatin behavior became prevalent. Here, we report that scaffold attachment factor A (SAF-A), originally identified as a structural nuclear protein, interacts with chromatin-associated RNAs (caRNAs) via its RGG domain to regulate human interphase chromatin structures in a transcription-dependent manner. Mechanistically, this is dependent on SAF-A’s AAA+ ATPase domain, which mediates cycles of protein oligomerization with caRNAs, in response to ATP binding and hydrolysis. SAF-A oligomerization decompacts large-scale chromatin structure while SAF-A loss or monomerization promotes aberrant chromosome folding and accumulation of genome damage. Our results show that SAF-A and caRNAs form a dynamic, transcriptionally responsive chromatin mesh that organizes large-scale chromosome structures and protects the genome from instability.

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Section: Introductionmentioning

confidence: 99%

SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs

Nozawa

Boteva

Soares

et al. 2017

Cell

194

216

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“…These so-called "heterogeneous nuclear RNAs" (hnRNAs) are transcribed from repetitive and heterochromatic regions, as well as from upward of 20% of all nonrepetitive regions in mammalian genomes (.10-fold higher by the same measure than the amount of transcription into mRNA). It was also known that 50% of hnRNAs are restricted to the nucleus and do not contain coding sequences (Holmes et al 1972;Pierpont and Yunis 1977;Lewin 1980, Chap. 25).…”

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confidence: 99%

Long Noncoding RNAs: Past, Present, and Future

2013

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Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes.T HE past several years have witnessed a steep rise of interest in the study of lncRNAs. Almost on a weekly basis, it seems that a new lncRNA is found to be up-or downregulated in a particular disease, or a new class of noncoding transcripts is uncovered by a transcriptomic study, or a new article heralds a paradigm shift that lncRNAs will bring to our understanding of biology. Without a doubt, the advent of sensitive, high-throughput genomic technologies such as microarrays and next-generation sequencing (NGS) has resulted in an unprecedented ability to detect novel transcripts, the vast majority of which seem not to be derived from annotated protein-coding genes. Despite this explosion of data, however, surprisingly little is known about how lncRNAs function, how many different types of lncRNAs exist, or even whether most of them carry biological significance.In this review, we focus on recently discovered lncRNAs of .200 nt, place these new discoveries in historical context, and outline areas where additional work is needed. The review does not cover "classic" ncRNAs such as ribosomal (r) RNAs, ribozymes, transfer (t)RNAs, small nuclear (sn)RNAs, small nucleolar (sno)RNAs, and telomere-associated RNAs (TERC, TERRA); nor does it cover small ncRNAs such as microRNAs (miRNAs), endogenous small interfering (endo-si)RNAs that participate in RNA interference (RNAi), and Piwi-associated (pi)RNAs. We refer readers to the many

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“…In this work, we report a link between nuclear AGO1, NEAT1 lncRNA, paraspeckles formation, and higher-order chromatin topological structure. The role of RNA as an essential component of the nuclear architecture has been recognized for a long time (Holmes et al 1972;Nickerson et al 1989). Recent paradigmatic works showed Xist (Cerase et al 2015) and Firre (Hacisuleyman et al 2014) lncRNAs to mediate both cisand trans-chromosomal interactions.…”

Section: Discussionmentioning

confidence: 99%

AGO1 in association with NEAT1 lncRNA contributes to nuclear and 3D chromatin architecture in human cells

Shuaib

Parsi

Kawaji

et al. 2019

Preprint

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Aside from their roles in the cytoplasm, RNA-interference components have been reported to localize also in the nucleus of human cells. In particular, AGO1 associates with active chromatin and appears to influence global gene expression. However, the mechanistic aspects remain elusive. Here, we identify AGO1 as a paraspeckle component that in combination with the NEAT1 lncRNA maintains 3D genome architecture. We demonstrate that AGO1 interacts with NEAT1 lncRNA and its depletion affects NEAT1 expression and the formation of paraspeckles. By Hi-C analysis in AGO1 knockdown cells, we observed global changes in chromatin organization, including TADs configuration, and A/B compartment mixing. Consistently, distinct groups of genes located within the differential interacting loci showed altered expression upon AGO1 depletion. NEAT1 knockout cells displayed similar changes in TADs and higher-order A/B compartmentalization. We propose that AGO1 in association with NEAT1 lncRNA can act as a scaffold that bridges chromatin and nuclear bodies to regulate genome organization and gene expression in human cells.

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Chromosomal RNA: Its Properties

Abstract: We describe the properties of a special class of RNA associated with chromatin. We discuss why this RNA should be considered a distinct class of RNA and not an artifactual degradation product of either transfer or ribosomal RNA.

Cited by 81 publications

References 17 publications

SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs

SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs

Long Noncoding RNAs: Past, Present, and Future

AGO1 in association with NEAT1 lncRNA contributes to nuclear and 3D chromatin architecture in human cells

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