The Role of Human Centromeric RNA in Chromosome Stability

Leclerc, Simon; Kitagawa, Katsumi

doi:10.3389/fmolb.2021.642732

Cited by 17 publications

(23 citation statements)

References 83 publications

(130 reference statements)

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“…In our data, centromeric RNAs fall in gene-free regions. As shown in Figures 8, RNAs These observations are in accordance with previous reports that the centromeric sequences have a repetitive nature (alpha-satellite tandem repeats) 42 . The centromeric expression signals of our RNA-seq data overlap with repeat markers including simple repeats (micro-satellites, Figure 8A-D).…”

Section: -Transcripts From Centromeric Regionssupporting

confidence: 92%

“…The copyright holder for this preprint this version posted October 14, 2021. ; https://doi.org/10.1101/2021.10.12.464167 doi: bioRxiv preprint These observations are in accordance with previous reports that the centromeric sequences have a repetitive nature (alpha-satellite tandem repeats) 42 . The centromeric expression signals of our RNA-seq data overlap with repeat markers including simple repeats (micro-satellites, Figure 8A-D).…”

Section: -Transcripts From Centromeric Regionssupporting

confidence: 91%

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The accumulation of lncRNAs in hybrid with DNA in patients with psoriasis reveals a decrease in the levels of RNase HII transcripts in the skin

Mehmetbeyoglu

Kianmehr

Borlu

et al. 2021

Preprint

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Long functional non-coding RNAs (lncRNAs) have been in the limelight in aging research because short telomeres are associated with higher levels of TERRA (Telomeric Repeat containing RNA). The genomic instability caused in Immune-mediated inflammatory diseases (IMID) especially in patients with psoriasis, which lead to short telomeres in psoriasis lesions, is a mechanism leading to cell aging. Research on the fraction of TERRA in hybrid with DNA offers avenues for new strategies. Skin samples were fractionated to obtain the RNA associated with DNA as a R-loop structure. TERRA analysis was performed by RT-qPCR and RNA-seq analysis. The higher amount of TERRA levels attached with each chromosome end was found with psoriasis patients. The increased levels of TERRA linked with telomeres correlate with the decrease in the RNase-HII transcript which means the unresolved DNA/RNA hybrids may ultimately facilitate the formation of skin lesions. LncRNAs have multiple molecular functions, including the regulation of heterochromatin, which controls genome stability and epigenome shaping and may be used as a trans-generational prognostic marker in patients with psoriasis.

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Section: -Transcripts From Centromeric Regionssupporting

confidence: 92%

Section: -Transcripts From Centromeric Regionssupporting

confidence: 91%

The accumulation of lncRNAs in hybrid with DNA in patients with psoriasis reveals a decrease in the levels of RNase HII transcripts in the skin

Mehmetbeyoglu

Kianmehr

Borlu

et al. 2021

Preprint

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“…On the other hand, the transcription of pericentromeric regions containing inactive chromatin is suppressed due to the presence of distinct epigenetic markers, which prevents transposon reactivation, carcinogenesis and disease [ 27 ]. Taken together, centromeric transcription and cenRNA are indispensable for proper centromere function and dysregulation of these results in chromosome instability or cancer [ 28 ].…”

Section: Building Blocks Of Chromosome Segregationmentioning

confidence: 99%

Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes

Pajpach

Shearwin-Whyatt

et al. 2021

Genes

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Segregation of chromosomes is a multistep process occurring both at mitosis and meiosis to ensure that daughter cells receive a complete set of genetic information. Critical components in the chromosome segregation include centromeres, kinetochores, components of sister chromatid and homologous chromosomes cohesion, microtubule organizing centres, and spindles. Based on the cytological work in the grasshopper Brachystola, it has been accepted for decades that segregation of homologs at meiosis is fundamentally random. This ensures that alleles on chromosomes have equal chance to be transmitted to progeny. At the same time mechanisms of meiotic drive and an increasing number of other examples of non-random segregation of autosomes and sex chromosomes provide insights into the underlying mechanisms of chromosome segregation but also question the textbook dogma of random chromosome segregation. Recent advances provide a better understanding of meiotic drive as a prominent force where cellular and chromosomal changes allow autosomes to bias their segregation. Less understood are mechanisms explaining observations that autosomal heteromorphism may cause biased segregation and regulate alternating segregation of multiple sex chromosome systems or translocation heterozygotes as an extreme case of non-random segregation. We speculate that molecular and cytological mechanisms of non-random segregation might be common in these cases and that there might be a continuous transition between random and non-random segregation which may play a role in the evolution of sexually antagonistic genes and sex chromosome evolution.

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“…However, centromere functions are epigenetically specified by the histone H3 variant CENP-A rather than via the DNA sequence (5,6). In addition, the transcription of non-coding RNA (ncRNA) at the centromere plays an important role in centromere function (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…However, centromere functions are epigenetically specified by the histone H3 variant CENP-A rather than via the DNA sequence ( 5 , 6 ). In addition, the transcription of noncoding RNA (ncRNA) at the centromere plays an important role in centromere function ( 7 , 8 , 9 , 10 , 11 ). Therefore, centromeric transcription is tightly regulated, and its dysregulation may lead to an impaired centromere function.…”

mentioning

confidence: 99%

CENP-B promotes the centromeric localization of ZFAT to control transcription of noncoding RNA

Ishikura

Yoshida

Hashimoto

et al. 2021

Journal of Biological Chemistry

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The centromere is a chromosomal locus that is essential for the accurate segregation of chromosomes during cell division. Transcription of noncoding RNA (ncRNA) at the centromere plays a crucial role in centromere function. The zinc-finger transcriptional regulator ZFAT binds to a specific 8-bp DNA sequence at the centromere, named the ZFAT box, to control ncRNA transcription. However, the precise molecular mechanisms by which ZFAT localizes to the centromere remain elusive. Here we show that the centromeric protein CENP-B is required for the centromeric localization of ZFAT to regulate ncRNA transcription. The ectopic expression of CENP-B induces the accumulation of both endogenous and ectopically expressed ZFAT protein at the centromere in human cells, suggesting that the centromeric localization of ZFAT requires the presence of CENP-B. Coimmunoprecipitation analysis reveals that ZFAT interacts with the acidic domain of CENP-B, and depletion of endogenous CENP-B reduces the centromeric levels of ZFAT protein, further supporting that CENP-B is required for the centromeric localization of ZFAT. In addition, knockdown of CENP-B significantly decreased the expression levels of ncRNA at the centromere where ZFAT regulates the transcription, suggesting that CENP-B is involved in the ZFAT-regulated centromeric ncRNA transcription. Thus, we concluded that CENP-B contributes to the establishment of the centromeric localization of ZFAT to regulate ncRNA transcription.

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The Role of Human Centromeric RNA in Chromosome Stability

Cited by 17 publications

References 83 publications

The accumulation of lncRNAs in hybrid with DNA in patients with psoriasis reveals a decrease in the levels of RNase HII transcripts in the skin

The accumulation of lncRNAs in hybrid with DNA in patients with psoriasis reveals a decrease in the levels of RNase HII transcripts in the skin

Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes

CENP-B promotes the centromeric localization of ZFAT to control transcription of noncoding RNA

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