Duration of the first steps of the human rRNA processing

Popov, Alexey A.; Smirnov, Evgeny; Kováčik, Ľubomír; Raška, Otakar; Hagen, Guy M.; Stixová, Lenka; Raška, Ivan

doi:10.4161/nucl.23985

Cited by 37 publications

(26 citation statements)

References 29 publications

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“…2A, +AMD), both the FU-and EU-labeled m-pre-rRNAs were greatly reduced. The residual FU-labeling observed after AMD treatment was most probably due to detection of pre-rRNAs synthesized during the 10 min before effective inhibition of rDNA transcription (Popov et al, 2013). More interestingly, the large decrease of these m-pre-rRNAs induced delocalization of fibrillarin from the chromosome periphery to the cytoplasm ( Fig.…”

Section: Resultsmentioning

confidence: 93%

Sharing the mitotic pre-ribosomal particles between daughter cells

Sirri

Jourdan

Hernandez‐Verdun

et al. 2016

Journal of Cell Science

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Ribosome biogenesis is a fundamental multistep process initiated by the synthesis of 90S pre-ribosomal particles in the nucleoli of higher eukaryotes. Even though synthesis of ribosomes stops during mitosis while nucleoli disappear, mitotic pre-ribosomal particles persist as observed in pre-nucleolar bodies (PNBs) during telophase. To further understand the relationship between the nucleolus and the PNBs, the presence and the fate of the mitotic pre-ribosomal particles during cell division were investigated. We demonstrate that the recently synthesized 45S precursor ribosomal RNAs ( pre-rRNAs) as well as the 32S and 30S pre-rRNAs are maintained during mitosis and associated with the chromosome periphery together with pre-rRNA processing factors. Maturation of the mitotic pre-ribosomal particles, as assessed by the stability of the mitotic pre-rRNAs, is transiently arrested during mitosis by a cyclin-dependent kinase (CDK)1-cyclin-B-dependent mechanism and can be restored by CDK inhibitor treatments. At the M-G1 transition, the resumption of mitotic prerRNA processing in PNBs does not induce the disappearance of PNBs; this only occurs when functional nucleoli reform. Strikingly, during their maturation process, mitotic pre-rRNAs localize in reforming nucleoli.

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Section: Resultsmentioning

confidence: 93%

Sharing the mitotic pre-ribosomal particles between daughter cells

Sirri

Jourdan

Hernandez‐Verdun

et al. 2016

Journal of Cell Science

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“…Quantification of rRNA amounts depends on synthesis and degradation rates. 47S has a very short half‐life time in the range of minutes (Popov et al , ) as compared to 18S and 28S that are stable for days (Defoiche et al , ). Therefore, 47S steady‐state measurements can be correlated with the synthesis rate of the precursor (before the cleavage of the 5′‐ETS), as done here.…”

Section: Methodsmentioning

confidence: 99%

Alu element‐containing RNAs maintain nucleolar structure and function

et al. 2015

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Non-coding RNAs play a key role in organizing the nucleus into functional subcompartments. By combining fluorescence microscopy and RNA deep-sequencing-based analysis, we found that RNA polymerase II transcripts originating from intronic Alu elements (aluRNAs) were enriched in the nucleolus. Antisense-oligo-mediated depletion of aluRNAs or drug-induced inhibition of RNA polymerase II activity disrupted nucleolar structure and impaired RNA polymerase I-dependent transcription of rRNA genes. In contrast, overexpression of a prototypic aluRNA sequence increased both nucleolus size and levels of pre-rRNA, suggesting a functional link between aluRNA, nucleolus integrity and pre-rRNA synthesis. Furthermore, we show that aluRNAs interact with nucleolin and target ectopic genomic loci to the nucleolus. Our study suggests an aluRNA-based mechanism that links RNA polymerase I and II activities and modulates nucleolar structure and rRNA production.

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“…The 5’ETS amplicon corresponds to the 47S pre-rRNA 5’ETS leader region that undergoes rapid processing providing best insight into nascent pre-rRNA levels [38,39]. The amplicons corresponding to the 5’ETS/18S junction or the ITS1 regions may also detect more stable intermediates of rRNA processing [38,39]. To normalize pre-rRNA changes, total levels of mature 18S rRNA were used.…”

Section: Resultsmentioning

confidence: 99%

RNA Polymerase 1 Is Transiently Regulated by Seizures and Plays a Role in a Pharmacological Kindling Model of Epilepsy

et al. 2018

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Ribosome biogenesis, including the RNA polymerase 1 (Pol1)-mediated transcription of rRNA, is regulated by the pro-epileptogenic mTOR pathway. Therefore, hippocampal Pol1 activity was examined in mouse models of epilepsy including kainic acid- and pilocarpine-induced status epilepticus (SE) as well as a single seizure in response to pentylenetetrazole (PTZ). Elevated 47S pre-rRNA levels were present acutely after induction of SE suggesting activation of Pol1. Conversely, after a single seizure, 47S pre-rRNA was transiently downregulated with increased levels of unprocessed 18S rRNA precursors in the cornu Ammonis (CA) region. At least in the dentate gyrus (DG), the pilocarpine SE-mediated transient activation of Pol1 did not translate into long-term changes of pre-rRNA levels or total ribosome content. Unaltered hippocampal ribosome content was also found after a 20-day PTZ kindling paradigm with increasing pro-convulsive effects of low dose PTZ that was injected every other day. However, after selectively deleting the essential Pol1 co-activator, transcription initiation factor-1A (Tif1a/Rrn3) from excitatory neurons, PTZ kindling was impaired while DG total ribosome content was moderately reduced and no major neurodegeneration was observed throughout the hippocampus. Therefore, Pol1 activity of excitatory neurons is required for PTZ kindling. As seizures affect ribosome biogenesis without long-term effects on the total ribosome content, such a requirement may be associated with a need to produce specialized ribosomes that promote pro-epileptic plasticity.

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Duration of the first steps of the human rRNA processing

Cited by 37 publications

References 29 publications

Sharing the mitotic pre-ribosomal particles between daughter cells

Sharing the mitotic pre-ribosomal particles between daughter cells

Alu element‐containing RNAs maintain nucleolar structure and function

RNA Polymerase 1 Is Transiently Regulated by Seizures and Plays a Role in a Pharmacological Kindling Model of Epilepsy

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