Phase separated ribosome-nascent chain complexes in genotoxic stress response

Assemblysomes are EDTA- and RNase-resistant ribonucleoprotein (RNP) complexes of paused ribosomes with protruding nascent polypeptide chains. They have been described in yeast and human cells for the proteasome subunit Rpt1, and the disordered N-terminal part of the nascent chain was found to be ind...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Szatmári Orsolya
Nagy-Miko Bence
Györkei Ádám
Varga Dániel
H. Kovács Bálint Barna
Igaz Nóra
Bognár Bence
Rázga Zsolt
Nagy Gábor
Zsindely Nóra
Bodai László
Papp Balázs
Erdélyi Miklós
Csontné Kiricsi Mónika
Blastyák András
Collart Martine A.
Boros Imre Miklós
Villanyi Zoltan
Dokumentumtípus: Cikk
Megjelent: 2023
Sorozat:RNA-A PUBLICATION OF THE RNA SOCIETY 29 No. 10
Tárgyszavak:
doi:10.1261/rna.079755.123

mtmt:34067381
Online Access:http://publicatio.bibl.u-szeged.hu/27910
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520 3 |a Assemblysomes are EDTA- and RNase-resistant ribonucleoprotein (RNP) complexes of paused ribosomes with protruding nascent polypeptide chains. They have been described in yeast and human cells for the proteasome subunit Rpt1, and the disordered N-terminal part of the nascent chain was found to be indispensable for the accumulation of the Rpt1-RNP into assemblysomes. Motivated by this, to find other assemblysome-associated RNPs we used bioinformatics to rank subunits of Saccharomyces cerevisiae protein complexes according to their N-terminal disorder propensity. The results revealed that gene products involved in DNA repair are enriched among the top candidates. The Sgs1 DNA helicase was chosen for experimental validation. We found that indeed nascent chains of Sgs1 form EDTA-resistant RNP condensates, assemblysomes by definition. Moreover, upon exposure to UV, SGS1 mRNA shifted from assemblysomes to polysomes, suggesting that external stimuli are regulators of assemblysome dynamics. We extended our studies to human cell lines. The BLM helicase, ortholog of yeast Sgs1, was identified upon sequencing assemblysome-associated RNAs from the MCF7 human breast cancer cell line, and mRNAs encoding DNA repair proteins were overall enriched. Using the radiation-resistant A549 cell line, we observed by transmission electron microscopy that 1,6-hexanediol, an agent known to disrupt phase-separated condensates, depletes ring ribosome structures compatible with assemblysomes from the cytoplasm of cells and makes the cells more sensitive to X-ray treatment. Taken together these findings suggest that assemblysomes may be a component of the DNA damage response from yeast to human. 
650 4 |a Biológiai tudományok 
700 0 2 |a Nagy-Miko Bence  |e aut 
700 0 2 |a Györkei Ádám  |e aut 
700 0 2 |a Varga Dániel  |e aut 
700 0 2 |a H. Kovács Bálint Barna  |e aut 
700 0 2 |a Igaz Nóra  |e aut 
700 0 2 |a Bognár Bence  |e aut 
700 0 2 |a Rázga Zsolt  |e aut 
700 0 2 |a Nagy Gábor  |e aut 
700 0 2 |a Zsindely Nóra  |e aut 
700 0 2 |a Bodai László  |e aut 
700 0 2 |a Papp Balázs  |e aut 
700 0 2 |a Erdélyi Miklós  |e aut 
700 0 2 |a Csontné Kiricsi Mónika  |e aut 
700 0 2 |a Blastyák András  |e aut 
700 0 2 |a Collart Martine A.  |e aut 
700 0 2 |a Boros Imre Miklós  |e aut 
700 0 2 |a Villanyi Zoltan  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/27910/3/34067381_megjelenet.pdf  |z Dokumentum-elérés  
856 4 0 |u http://publicatio.bibl.u-szeged.hu/27910/1/RNA-2023-Nemeth-Szatmari-rna.079755.1231.pdf  |z Dokumentum-elérés