RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops

Feretzaki, Marianna; Pospíšilová, Michaela; Fernandes, Rita Valador; Lunardi, T.; Krejčí, Lumír; Lingner, Joachim

doi:10.1038/s41586-020-2815-6

Cited by 158 publications

(172 citation statements)

References 28 publications

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“…Here, we show that DNA:RNA hybrids involving telomeric repeats are more abundant in ALT cells compared with non-ALT cells. These results are consistent with previous reports [ 7 ], and provide a broader view on the landscape of endogenous telomeric DNA:RNA hybrids to include endogenous TTAGGG repeats, which are the most critical part of the telomeres involved in hybrid formation [ 24 , 30 ].…”

Section: Discussionsupporting

confidence: 93%

Detection of Telomeric DNA:RNA Hybrids Using TeloDRIP-qPCR

Rosso

Fagagna

2020

IJMS

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Because of their intrinsic characteristics, telomeres are genomic loci that pose significant problems during the replication of the genome. In particular, it has been observed that telomeres that are maintained in cancer cells by the alternative mechanism of the lengthening of telomeres (ALT) harbor higher levels of replicative stress compared with telomerase-positive cancer cells. R-loops are three-stranded structures formed by a DNA:RNA hybrid and a displaced ssDNA. Emerging evidence suggests that controlling the levels of R-loops at ALT telomeres is critical for telomere maintenance. In fact, on the one hand, they favor telomere recombination, but on the other, they are a source of detrimental replicative stress. DRIP (DNA:RNA immunoprecipitation) is the main technique used for the detection of R-loops, and it is based on the use of the S9.6 antibody, which recognizes preferentially DNA:RNA hybrids in a sequence-independent manner. The detection of DNA:RNA hybrids in repetitive sequences such as telomeres requires some additional precautions as a result of their repetitive nature. Here, we share an optimized protocol for the detection of telomeric DNA:RNA hybrids, and we demonstrate its application in an ALT and in a telomerase-positive cell line. We demonstrate that ALT telomeres bear higher levels of DNA:RNA hybrids, and we propose this method as a reliable way to detect them in telomeres.

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Section: Discussionsupporting

confidence: 93%

Detection of Telomeric DNA:RNA Hybrids Using TeloDRIP-qPCR

Rosso

Fagagna

2020

IJMS

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“…TERRAs are recruited to telomeres where they form DNA-RNA hybrid R-loops. This R-loop formation regulates telomere maintenance through interactions with chromatin modifiers, telomerase, and promoting DNA repair (166,167). TERRAs also facilitate telomere replication and promote the assembly of shelterin proteins (168,169).…”

Section: Terra (Telomere Repeat-containing Rna)mentioning

confidence: 99%

Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

Omote

Sauler

2020

Front. Med.

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Cellular senescence is a cell fate implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Cellular senescence occurs in response to cellular stressors such as oxidative stress, DNA damage, telomere shortening, and mitochondrial dysfunction. Whether these stresses induce cellular senescence or an alternative cell fate depends on the type and magnitude of cellular stress, but also on intrinsic factors regulating the cellular stress response. Non-coding RNAs, including both microRNAs and long non-coding RNAs, are key regulators of cellular stress responses and susceptibility to cellular senescence. In this review, we will discuss cellular mechanisms that contribute to senescence in IPF and COPD and highlight recent advances in our understanding of how these processes are influenced by non-coding RNAs. We will also discuss the potential therapeutic role for targeting non-coding RNAs to treat these chronic lung diseases.

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“…Long noncoding RNAs (lncRNAs) constitute a large fraction of the transcriptome that does not encode proteins [14], and play important roles in various biological processes, such as genome stability [15], vernalization [16], telomere maintenance [17], transcriptional activation [18], and other developmental processes [19]. Various transcriptome studies have revealed that pervasive transcription from noncoding transcripts can give rise to functional lncRNAs [20].…”

Section: Introductionmentioning

confidence: 99%

Identification of long noncoding natural antisense transcripts (lncNATs) correlated with drought stress response in wild rice (Oryza nivara)

Zhang

et al. 2021

Preprint

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Background Wild rice, including Oryza nivara and Oryza rufipogon, which are considered as the ancestors of Asian cultivated rice (Oryza sativa L.), possess high genetic diversity and serve as a crucial resource for breeding novel cultivars of cultivated rice. Although many rice domestication related traits, such as seed shattering and plant architecture, have been intensively studied at the phenotypic and genomic levels, further investigation is needed to understand the molecular basis of phenotypic differences between cultivated and wild rice. Drought stress is one of the most severe abiotic stresses affecting rice growth and production. Adaptation to drought stress involves a cascade of genes and regulatory factors that form complex networks. Long noncoding natural antisense transcripts (lncNATs), a class of long noncoding RNAs (lncRNAs), regulate the corresponding sense transcripts and play an important role in plant growth and development. However, the contribution of lncNATs to drought stress response in wild rice remains largely unknown. Results Here, we conducted strand-specific RNA sequencing (ssRNA-seq) analysis of Nipponbare (O. sativa ssp. japonica) and two O. nivara accessions (BJ89 and BJ278) to determine the role of lncNATs in drought stress response in wild rice. A total of 1,246 lncRNAs were identified, including 1,091 coding–noncoding NAT pairs, of which 50 were expressed only in Nipponbare, and 77 were expressed only in BJ89 and/or BJ278. Of the 1,091 coding–noncoding NAT pairs, 240 were differentially expressed between control and drought stress conditions. Among these 240 NAT pairs, 12 were detected only in Nipponbare, and 187 were detected uniquely in O. nivara. Furthermore, 10 of the 240 coding–noncoding NAT pairs were correlated with genes previously demonstrated to be involved in stress response; among these, nine pairs were uniquely found in O. nivara, and one pair was shared between O. nivara and Nipponbare. Conclusion We identified lncNATs associated with drought stress response in cultivated rice and O. nivara. These results will improve our understanding of the function of lncNATs in drought tolerance and accelerate rice breeding.

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RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops

Cited by 158 publications

References 28 publications

Detection of Telomeric DNA:RNA Hybrids Using TeloDRIP-qPCR

Detection of Telomeric DNA:RNA Hybrids Using TeloDRIP-qPCR

Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

Identification of long noncoding natural antisense transcripts (lncNATs) correlated with drought stress response in wild rice (Oryza nivara)

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