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SFPQ and NONO suppress RNA:DNA-hybrid-related telomere instability.
Nature Communications ( IF 14.7 ) Pub Date : 2019-03-01 , DOI: 10.1038/s41467-019-08863-1
Eleonora Petti 1, 2, 3 , Valentina Buemi 1, 2 , Antonina Zappone 1, 2 , Odessa Schillaci 1 , Pamela Veneziano Broccia 1, 2 , Roberto Dinami 1, 2, 3 , Silvia Matteoni 4 , Roberta Benetti 5, 6 , Stefan Schoeftner 1, 2
Nature Communications ( IF 14.7 ) Pub Date : 2019-03-01 , DOI: 10.1038/s41467-019-08863-1
Eleonora Petti 1, 2, 3 , Valentina Buemi 1, 2 , Antonina Zappone 1, 2 , Odessa Schillaci 1 , Pamela Veneziano Broccia 1, 2 , Roberto Dinami 1, 2, 3 , Silvia Matteoni 4 , Roberta Benetti 5, 6 , Stefan Schoeftner 1, 2
Affiliation
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In vertebrates, the telomere repeat containing long, non-coding RNA TERRA is prone to form RNA:DNA hybrids at telomeres. This results in the formation of R-loop structures, replication stress and telomere instability, but also contributes to alternative lengthening of telomeres (ALT). Here, we identify the TERRA binding proteins NONO and SFPQ as novel regulators of RNA:DNA hybrid related telomere instability. NONO and SFPQ locate at telomeres and have a common role in suppressing RNA:DNA hybrids and replication defects at telomeres. NONO and SFPQ act as heterodimers to suppress fragility and homologous recombination at telomeres, respectively. Combining increased telomere fragility with unleashing telomere recombination upon NONO/SFPQ loss of function causes massive recombination events, involving 35% of telomeres in ALT cells. Our data identify the RNA binding proteins SFPQ and NONO as novel regulators at telomeres that collaborate to ensure telomere integrity by suppressing telomere fragility and homologous recombination triggered by RNA:DNA hybrids.
中文翻译：
SFPQ和NONO抑制RNA：DNA杂交相关端粒的不稳定性。
在脊椎动物中，含有长的非编码RNA TERRA的端粒重复序列易于在端粒上形成RNA：DNA杂种。这导致R环结构的形成，复制应力和端粒的不稳定性，但也有助于端粒（ALT）的替代性延长。在这里，我们将TERRA结合蛋白NONO和SFPQ鉴定为RNA：DNA杂种相关端粒不稳定性的新型调节剂。NONO和SFPQ位于端粒，并在抑制RNA：DNA杂种和端粒复制缺陷中起着共同的作用。NONO和SFPQ分别作为异二聚体来抑制端粒的脆性和同源重组。在NONO / SFPQ功能丧失时将增加的端粒脆性与释放的端粒重组结合在一起会引起大量的重组事件，涉及ALT细胞中35％的端粒。
更新日期：2019-03-01
中文翻译：
SFPQ和NONO抑制RNA：DNA杂交相关端粒的不稳定性。
在脊椎动物中，含有长的非编码RNA TERRA的端粒重复序列易于在端粒上形成RNA：DNA杂种。这导致R环结构的形成，复制应力和端粒的不稳定性，但也有助于端粒（ALT）的替代性延长。在这里，我们将TERRA结合蛋白NONO和SFPQ鉴定为RNA：DNA杂种相关端粒不稳定性的新型调节剂。NONO和SFPQ位于端粒，并在抑制RNA：DNA杂种和端粒复制缺陷中起着共同的作用。NONO和SFPQ分别作为异二聚体来抑制端粒的脆性和同源重组。在NONO / SFPQ功能丧失时将增加的端粒脆性与释放的端粒重组结合在一起会引起大量的重组事件，涉及ALT细胞中35％的端粒。
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