Ribosomal RNA regulates chromosome clustering during mitosis

Ma, Kai; Luo, Ming; Xie, Guanglei; Wang, Xi; Li, Qilin; Gao, Lei; Yu, Hongtao; Yu, Xiaochun

doi:10.1038/s41421-022-00400-7

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…On the other hand, our findings support the notion that Ki-67’s interaction with RNA is key to phase separation and chromosome clustering. Several studies suggested that Ki-67 interacts either directly or indirectly with RNA: Recent reports showed that Ki-67 depletion caused loss of newly synthesized RNAs from chromosomes in early mitosis 7 , that recombinantly expressed fragments of Ki-67 such as the fork-head associated (FHA) domain or three tandem repeats pulled down pre-rRNAs from total RNA 26 , and that the FHA domain interacted with the putative RNA-binding protein NIFK 27 . Since the latter interaction was dependent on mitotic phosphorylation, it is, however, unlikely that NIFK binding contributes to RNA recruitment during mitotic exit.…”

Section: Discussionmentioning

confidence: 99%

A liquid-like coat mediates chromosome clustering during mitotic exit

Hernandez-Armendariz,

Sorichetti,

Hayashi

et al. 2023

Preprint

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SummaryThe individualization of chromosomes during early mitosis and their clustering upon exit from cell division are two key transitions that ensure efficient segregation of eukaryotic chromosomes. Both processes are regulated by the surfactant-like protein Ki-67, but how Ki-67 achieves these diametric functions has remained unknown. Here, we report that Ki-67 radically switches from a chromosome repellent to a chromosome attractant during anaphase. We show that Ki-67 dephosphorylation during mitotic exit and the simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface. Experiments and coarse-grained simulations support a model in which the coalescence of chromosome surfaces driven by phase separation promote clustering of chromosomes. Our study reveals how the switch of Ki-67 from a surfactant to a liquid-like condensed phase can generate the mechanical forces during genome segregation that are required for re-establishing nuclear-cytoplasmic compartmentalization after mitosis.

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Section: Discussionmentioning

confidence: 99%

A liquid-like coat mediates chromosome clustering during mitotic exit

Hernandez-Armendariz,

Sorichetti,

Hayashi

et al. 2023

Preprint

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“…The RT-PCR products were visualized by agarose (2%) gel electrophoresis. Subcellular fractions were confirmed by respective fraction markers: Gapdh and RNA18S (cytoplasmic markers), Malat1 (nuclear markers), and RNA45S (chromatin markers), since 45S rRNA is chromosome-associated [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

A Novel Cis-Regulatory lncRNA, Kalnc2, Downregulates Kalrn Protein-Coding Transcripts in Mouse Neuronal Cells

Pal

Chaubey

Tanwar

et al. 2023

ncRNA

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The KALRN gene encodes several multi-domain protein isoforms that localize to neuronal synapses, conferring the ability to grow and retract dendritic spines and shaping axonal outgrowth, dendrite morphology, and dendritic spine re-modeling. The KALRN genomic locus is implicated in several neurodevelopmental and neuropsychiatric diseases, including autism, schizophrenia, bipolar disease, and intellectual disability. We have previously shown that a novel brain-specific long non-coding RNA (lncRNA) arising from the 5′ end of the kalrna gene, called durga, regulates neuronal morphology in zebrafish. Here, we characterized mammalian Kalrn loci, annotating and experimentally validating multiple novel non-coding RNAs, including linear and circular variants. Comparing the mouse and human loci, we show that certain non-coding RNAs and Kalrn protein-coding isoforms arising from the locus show similar expression dynamics during development. In humans, mice, and zebrafish, the 5′ end of the Kalrn locus gives rise to a chromatin-associated lncRNA that is present in adult ovaries, besides being expressed during brain development and enriched in certain regions of the adult brain. Ectopic expression of this lncRNA led to the downregulation of all the major Kalrn mRNA isoforms. We propose that this lncRNA arising from the 5′ end of the Kalrn locus is functionally the mammalian ortholog of zebrafish lncRNA durga.

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“…Cells were lysed using NETN100 buffer (25 mM Tris-HCl pH 7.5, 100 mM NaCl, 0.5% Nonidet P-40, 1 U/μl RNase inhibitor, 100 mM PMSF) ( 26 , 27 ). The lysate was centrifuged at 2000 g at 4°C for 20 min to separate the NETN100 soluble and pellet fractions.…”

Section: Methodsmentioning

confidence: 99%

Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA

Ma,

Wang,

et al. 2023

Nucleic Acids Research

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The exonuclease ISG20L2 has been initially characterized for its role in the mammalian 5.8S rRNA 3′ end maturation, specifically in the cleavage of ITS2 of 12S precursor ribosomal RNA (pre-rRNA). Here, we show that human ISG20L2 is also involved in 18S pre-rRNA maturation through removing the ITS1 region, and contributes to ribosomal biogenesis and cell proliferation. Furthermore, we determined the crystal structure of the ISG20L2 nuclease domain at 2.9 Å resolution. It exhibits the typical αβα fold of the DEDD 3′-5′ exonuclease with a catalytic pocket located in the hollow near the center. The catalytic residues Asp183, Glu185, Asp267, His322 and Asp327 constitute the DEDDh motif in ISG20L2. The active pocket represents conformational flexibility in the absence of an RNA substrate. Using structural superposition and mutagenesis assay, we mapped RNA substrate binding residues in ISG20L2. Finally, cellular assays revealed that ISG20L2 is aberrantly up-regulated in colon adenocarcinoma and promotes colon cancer cell proliferation through regulating ribosome biogenesis. Together, these results reveal that ISG20L2 is a new enzymatic member for 18S pre-rRNA maturation, provide insights into the mechanism of ISG20L2 underlying pre-rRNA processing, and suggest that ISG20L2 is a potential therapeutic target for colon adenocarcinoma.

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Ribosomal RNA regulates chromosome clustering during mitosis

Cited by 13 publications

References 34 publications

A liquid-like coat mediates chromosome clustering during mitotic exit

A liquid-like coat mediates chromosome clustering during mitotic exit

A Novel Cis-Regulatory lncRNA, Kalnc2, Downregulates Kalrn Protein-Coding Transcripts in Mouse Neuronal Cells

Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA

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