RAD51-dependent recruitment of TERRA lncRNA to telomeres
through R-loops

J 2020

RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops

FERETZAKI, Marianna; Michaela POSPÍŠILOVÁ; Rita VALADOR FERNANDES; Thomas LUNARDI; Lumír KREJČÍ et al.

Základní údaje

Originální název

RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops

Autoři

FERETZAKI, Marianna; Michaela POSPÍŠILOVÁ; Rita VALADOR FERNANDES; Thomas LUNARDI; Lumír KREJČÍ a Joachim LINGNER

Vydání

Nature, Berlin, Nature Research, 2020, 0028-0836

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10603 Genetics and heredity

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 49.962

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/20:00114561

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

RAD51; TERRA lncRNA; R-loops

Štítky

14110513, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 30. 4. 2021 08:45, Mgr. Tereza Miškechová

Anotace

V originále

Telomeres- repeated, noncoding nucleotide motifs and associated proteins that are found at the ends of eukaryotic chromosomes—mediate genome stability and determine cellular lifespan. Telomeric-repeat-containing RNA (TERRA) is a class of long noncoding RNAs (lncRNAs) that are transcribed from chromosome ends; these RNAs in turn regulate telomeric chromatin structure and telomere maintenance through the telomere-extending enzyme telomerase and homology-directed DNA repair. The mechanisms by which TERRA is recruited to chromosome ends remain poorly defined. Here we develop a reporter system with which to dissect the underlying mechanisms, and show that the UUAGGG repeats of TERRA are both necessary and sufficient to target TERRA to chromosome ends. TERRA preferentially associates with short telomeres through the formation of telomeric DNA–RNA hybrid (R-loop) structures that can form in trans. Telomere association and R-loop formation trigger telomere fragility and are promoted by the recombinase RAD51 and its interacting partner BRCA2, but counteracted by the RNA-surveillance factors RNaseH1 and TRF1. RAD51 physically interacts with TERRA and catalyses R-loop formation with TERRA in vitro, suggesting a direct involvement of this DNA recombinase in the recruitment of TERRA by strand invasion. Together, our findings reveal a RAD51-dependent pathway that governs TERRA-mediated R-loop formation after transcription, providing a mechanism for the recruitment of lncRNAs to new loci in trans.

Návaznosti

EF16_025/0007381, projekt VaV

Název: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

GA17-17720S, projekt VaV

Název: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Grantová agentura ČR, Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

MUNI/A/0951/2019, interní kód MU

Název: Buněčná a molekulární biologie pro Biomedicínské vědy

Investor: Masarykova univerzita, Buněčná a molekulární biologie pro Biomedicínské vědy, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

206292/E/17/Z, interní kód MU

Název: Mechanics and execution of homologous recombination - biophysics to the organism

Investor: Wellcome Trust, Mechanics and execution of homologous recombination - biophysics to the organism

Přiložené soubory

RAD51-dependent_recruitment_of_TERRA_lncRNA_to_telomeres_through_R-loops.pdf Verze souboru

Citovat

FERETZAKI, Marianna; Michaela POSPÍŠILOVÁ; Rita VALADOR FERNANDES; Thomas LUNARDI; Lumír KREJČÍ a Joachim LINGNER. RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops. Nature. Berlin: Nature Research, 2020, roč. 587, č. 7833, s. 303-308. ISSN 0028-0836. Dostupné z: https://doi.org/10.1038/s41586-020-2815-6.

@article{1707497,
   author = {Feretzaki, Marianna and Pospíšilová, Michaela and Valador Fernandes, Rita and Lunardi, Thomas and Krejčí, Lumír and Lingner, Joachim},
   article_location = {Berlin},
   article_number = {7833},
   doi = {https://doi.org/10.1038/s41586-020-2815-6},
   keywords = {RAD51; TERRA lncRNA; R-loops},
   language = {eng},
   issn = {0028-0836},
   journal = {Nature},
   title = {RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops},
   url = {https://www.nature.com/articles/s41586-020-2815-6},
   volume = {587},
   year = {2020}
}

TY  - JOUR
ID  - 1707497
AU  - Feretzaki, Marianna - Pospíšilová, Michaela - Valador Fernandes, Rita - Lunardi, Thomas - Krejčí, Lumír - Lingner, Joachim
PY  - 2020
TI  - RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops
JF  - Nature
VL  - 587
IS  - 7833
SP  - 303-308
EP  - 303-308
PB  - Nature Research
SN  - 00280836
KW  - RAD51
KW  - TERRA lncRNA
KW  - R-loops
UR  - https://www.nature.com/articles/s41586-020-2815-6
L2  - https://www.nature.com/articles/s41586-020-2815-6
N2  - Telomeres- repeated, noncoding nucleotide motifs and associated proteins that are found at the ends of eukaryotic chromosomes—mediate genome stability and determine cellular lifespan. Telomeric-repeat-containing RNA (TERRA) is a class of long noncoding RNAs (lncRNAs) that are transcribed from chromosome ends; these RNAs in turn regulate telomeric chromatin structure and telomere maintenance through the telomere-extending enzyme telomerase and homology-directed DNA repair. The mechanisms by which TERRA is recruited to chromosome ends remain poorly defined. Here we develop a reporter system with which to dissect the underlying mechanisms, and show that the UUAGGG repeats of TERRA are both necessary and sufficient to target TERRA to chromosome ends. TERRA preferentially associates with short telomeres through the formation of telomeric DNA–RNA hybrid (R-loop) structures that can form in trans. Telomere association and R-loop formation trigger telomere fragility and are promoted by the recombinase RAD51 and its interacting partner BRCA2, but counteracted by the RNA-surveillance factors RNaseH1 and TRF1. RAD51 physically interacts with TERRA and catalyses R-loop formation with TERRA in vitro, suggesting a direct involvement of this DNA recombinase in the recruitment of TERRA by strand invasion. Together, our findings reveal a RAD51-dependent pathway that governs TERRA-mediated R-loop formation after transcription, providing a mechanism for the recruitment of lncRNAs to new loci in trans.
ER  -

FERETZAKI, Marianna; Michaela POSPÍŠILOVÁ; Rita VALADOR FERNANDES; Thomas LUNARDI; Lumír KREJČÍ a Joachim LINGNER. RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops. \textit{Nature}. Berlin: Nature Research, 2020, roč.~587, č.~7833, s.~303-308. ISSN~0028-0836. Dostupné z: https://doi.org/10.1038/s41586-020-2815-6.

Přehled o publikaci