Abundance of Ribosomal RNA Gene Copies Maintains Genome Integrity

Ide, Satoru; Miyazaki, T.; Maki, Hisaji; Kobayashi, Takehiko

doi:10.1126/science.1179044

Cited by 265 publications

(313 citation statements)

References 20 publications

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“…TOR inhibition can alter the rate of marker loss from the rDNA (23, 24); however, this occurs through the BIR pathway, which acts primarily to homogenize rDNA sequences, and it is not clear why rDNA homogenization should respond to the environment. In contrast, cells with suboptimal rDNA copy number are forced to up-regulate RNA pol I transcription to maintain ribosome synthesis, and rDNA amplification is a logical response in this situation; although ribosome synthesis can be enhanced temporarily by increasing RNA pol I transcription, this strategy is harmful in the long term (22,40). Controlled rDNA amplification is therefore a response to available nutrients being in excess compared with ribosome synthesis capacity.…”

Section: Discussionmentioning

confidence: 99%

Regulation of ribosomal DNA amplification by the TOR pathway

Jack

Cruz

Hull

et al. 2015

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

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Repeated regions are widespread in eukaryotic genomes, and key functional elements such as the ribosomal DNA tend to be formed of high copy repeated sequences organized in tandem arrays. In general, high copy repeats are remarkably stable, but a number of organisms display rapid ribosomal DNA amplification at specific times or under specific conditions. Here we demonstrate that target of rapamycin (TOR) signaling stimulates ribosomal DNA amplification in budding yeast, linking external nutrient availability to ribosomal DNA copy number. We show that ribosomal DNA amplification is regulated by three histone deacetylases: Sir2, Hst3, and Hst4. These enzymes control homologous recombination-dependent and nonhomologous recombination-dependent amplification pathways that act in concert to mediate rapid, directional ribosomal DNA copy number change. Amplification is completely repressed by rapamycin, an inhibitor of the nutrientresponsive TOR pathway; this effect is separable from growth rate and is mediated directly through Sir2, Hst3, and Hst4. Caloric restriction is known to up-regulate expression of nicotinamidase Pnc1, an enzyme that enhances Sir2, Hst3, and Hst4 activity. In contrast, normal glucose concentrations stretch the ribosome synthesis capacity of cells with low ribosomal DNA copy number, and we find that these cells show a previously unrecognized transcriptional response to caloric excess by reducing PNC1 expression. PNC1 down-regulation forms a key element in the control of ribosomal DNA amplification as overexpression of PNC1 substantially reduces ribosomal DNA amplification rate. Our results reveal how a signaling pathway can orchestrate specific genome changes and demonstrate that the copy number of repetitive DNA can be altered to suit environmental conditions. ribosomal DNA | homologous recombination | Sir2 | copy number variation | TOR

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Section: Discussionmentioning

confidence: 99%

Regulation of ribosomal DNA amplification by the TOR pathway

Jack

Cruz

Hull

et al. 2015

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

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“…In contrast to this finding, the copy number of rRNA genes in S. japonica seems not very appropriate for its genome size of about 545 Mb (Ye et al 2015), although the copy number still stands within the range of the available data from algae (Table 3). In these studies on the estimation of yeast rRNA gene copy number, Ide et al (2010) and Kobayashi (2011) found that the loss of these repeats in yeast cells confers sensitivity to DNA damage caused by mutagens such as UV radiation. Taking this into consideration and the fact that S. japonica can survive under medium irradiance of no more than 30% of the water surface solar irradiance (Fei et al 1989), which is generally accepted as the result of natural selection and adaptation to low light in the sub-littoral region (Häder and Figueroa 1997), the low copies of rDNA serves as a possible explanation why this particular kelp species is unable to tolerate high irradiance.…”

Section: Discussionmentioning

confidence: 99%

Characterization and physical mapping of nuclear ribosomal RNA (rRNA) genes in the haploid gametophytes of Saccharina japonica (Phaeophyta)

et al. 2017

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Nuclear tandemly repeated ribosomal RNA genes (18S-5.8S-25S rDNA and 5S rDNA) have been proven to be excellent cytogenetic markers for karyotype analysis of various higher plants by using the fluorescence in situ hybridization (FISH) technique. To illustrate physical mapping of these rDNAs in brown seaweed, Saccharina japonica, chromosomes, an approximately 5400-bp transcription unit of 18S-5.8S-25S rDNA was assembled by cloning the 25S rDNA after paired-end sequencing of two screened clones from a bacterial artificial chromosome library of kelp gametophytes. In contrast to the conserved 18S-5.8S-25S rDNA and ITS1 in S. japonica, the 245-bp ITS2 was variable in sequence. The cloned 5S rDNA revealed that the 120-bp conserved coding region was separated by a diverse intergenic spacer sequence that were 250, 445, 905, or 1335 bp in length. On average, the 18S-5.8S-25S rDNA of kelp female and male gametophytes had 45 and 41 copies per haploid genome, respectively, as detected by quantitative real-time PCR, whereas the 5S rDNA had 2590 and 2648 copies, respectively. Southern hybridization with labeled probes of 18S rDNA or 5S rDNA demonstrated that kelp gametophytes possessed only one locus each of the 18S-5.8S-25S or 5S rDNAs. This was further confirmed by FISH analysis using the same labeled probes, thus illustrating that 18S-5.8S-25S rDNA is located at the intercalary region of chromosome 23, whereas 5S rDNA at the sub-telomeric region of chromosomes 27. The localization of these rDNAs using the FISH technique has facilitated the identification of individual chromosomes and karyotype analysis of this kelp.

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“…Flanking sequences of the non-functional insert suggest that the insertion occurred in a 26S ribosomal RNA (rRNA) gene. Since rRNA genes are present in several copies in the genome (Ide et al, 2010), disruption of a single copy is unlikely to have an effect on the characteristics of the plant.…”

Section: Summary Of the Previous Evaluation Of Event Mon 531 Includimentioning

confidence: 99%

Scientific Opinion on applications (EFSA-GMO-UK-2008-57 and EFSA-GMO-RX-MON15985) for the placing on the market of insect-resistant genetically modified cotton MON 15985 for food and feed uses, import and processing, and for the renewal of authorisation o

Arpaia¹,

Birch²,

Chesson³

et al. 2014

EFSA Journal

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Cotton MON 15985 was developed by biolistic transformation of cotton MON 531 to express Cry2Ab2 and GUS in addition to the Cry1Ac and NPTII proteins. Cry proteins in MON 15985 confer resistance to major lepidopteran cotton pests, whereas the GUS and NPTII proteins were used as markers during product development. Molecular characterisation of MON 15985 did not give rise to safety issues. The EFSA GMO Panel could not conclude on the potential occurrence of unintended effects for agronomic and phenotypic characteristics owing to data limitations. Compositional data gave no indication of unintended effects for which further assessment was needed. The Panel concludes that cotton MON 15985, as described in these applications, is as safe and nutritious as its conventional counterpart and other non-genetically modified varieties, and considers it unlikely that the overall allergenicity of the whole plant is changed. Environmental risk assessment was restricted to the exposure through faecal material from animals fed with cotton products of MON 15985 and its accidental spillage. Following a weight of evidence approach and considering the poor ability of cotton to survive outside cultivated land, despite the agronomic and phenotypic data limitations, the Panel concludes that there is very low likelihood of any adverse environmental impacts. The aadA and oriV sequences in MON 15985 may facilitate the stabilisation of nptII through double homologous recombination. However, considering the limited presence of intact DNA from MON 15985 in feed and the limited occurrence of horizontal transfer of DNA from plant material to bacteria, the Panel concludes that it is highly unlikely that nptII from MON 15985 will be transferred to bacteria. Since both EFSA-GMO-UK-2008-57 and EFSA-GMO-RX-MON15985 cover cotton MON 15985, the EFSA GMO Panel provides a single scientific opinion, valid for both applications.The EFSA GMO Panel evaluated cotton MON 15985 with reference to the scope and appropriate principles described in its guidance documents for the risk assessment of genetically modified (GM) plants and derived food and feed (EFSA, 2006a; EFSA GMO Panel, 2011a), environmental risk assessment (ERA) (EFSA GMO Panel, 2010a) and for renewal of authorisations of existing GMO products lawfully placed on the market (EFSA, 2006b). The scientific evaluation of the risk assessment included molecular characterisation of the inserted DNA and analysis of the expression of the corresponding proteins. An evaluation of the comparative analyses of compositional, agronomic and phenotypic characteristics was undertaken, and the safety of the newly expressed proteins and the whole food/feed was evaluated with respect to potential toxicity, allergenicity and nutritional wholesomeness. An evaluation of environmental impacts and the post-market environmental monitoring (PMEM) plan was also undertaken.The scope of applications EFSA-GMO-UK-2008-57 and EFSA-GMO-RX-MON15985 covers the MON 15985 event in cotton species Gossypium hirsutum L. and G. barba...

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Abundance of Ribosomal RNA Gene Copies Maintains Genome Integrity

Cited by 265 publications

References 20 publications

Regulation of ribosomal DNA amplification by the TOR pathway

Regulation of ribosomal DNA amplification by the TOR pathway

Characterization and physical mapping of nuclear ribosomal RNA (rRNA) genes in the haploid gametophytes of Saccharina japonica (Phaeophyta)

Scientific Opinion on applications (EFSA-GMO-UK-2008-57 and EFSA-GMO-RX-MON15985) for the placing on the market of insect-resistant genetically modified cotton MON 15985 for food and feed uses, import and processing, and for the renewal of authorisation o

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