SFPQ and NONO suppress RNA:DNA-hybrid-related telomere instability

Petti, Eleonora; Buemi, Valentina; Zappone, Antonina; Schillaci, Odessa; Broccia, Pamela Veneziano; Dinami, Roberto; Matteoni, Silvia; Benetti, Roberta; Schoeftner, Stefan

doi:10.1038/s41467-019-08863-1

Cited by 97 publications

(89 citation statements)

References 56 publications

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“…Some of the proteins bound to TERRA or RNA:DNA hybrids may act to reduce replication stress and suppress ALT. For example, TERRA -binding proteins SFPQ and NONO suppress telomeric RNA:DNA hybrids, and depletion of SFPQ increases APBs and telomere recombination in ALT + cells [80].…”

Section: Regulatory Circuitries Of Altmentioning

confidence: 99%

Alternative lengthening of telomeres: from molecular mechanisms to therapeutic outlooks

2020

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To escape replicative senescence, cancer cells have to overcome telomere attrition during DNA replication. Most of cancers rely on telomerase to extend and maintain telomeres, but 4-11% of cancers use a homologous recombination-based pathway called alternative lengthening of telomeres (ALT). ALT is prevalent in cancers from the mesenchymal origin and usually associates with poor clinical outcome. Given its critical role in protecting telomeres and genomic integrity in tumor cells, ALT is an Achilles heel of tumors and an attractive target for cancer therapy. Here, we review the recent progress in the mechanistic studies of ALT, and discuss the emerging therapeutic strategies to target ALT-positive cancers.

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Section: Regulatory Circuitries Of Altmentioning

confidence: 99%

Alternative lengthening of telomeres: from molecular mechanisms to therapeutic outlooks

2020

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“…More recently, further involvement of SFPQ in the maintenance of genome stability has been demonstrated in relation to telomere maintenance, where the SFPQ/NONO heterodimer has been identified as a novel regulator at telomeres [ 46 ] ( Figure 2 E). It was shown that loss of SFPQ/NONO results in a significant increase in telomere recombination events and rapid alterations in telomere length in both telomerase-positive and negative cells.…”

Section: The Rna-binding Protein Sfpqmentioning

confidence: 99%

The Emerging Role of the RNA-Binding Protein SFPQ in Neuronal Function and Neurodegeneration

Lim

James

Huang

et al. 2020

IJMS

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RNA-binding proteins (RBPs) are a class of proteins known for their diverse roles in RNA biogenesis, from regulating transcriptional processes in the nucleus to facilitating translation in the cytoplasm. With higher demand for RNA metabolism in the nervous system, RBP misregulation has been linked to a wide range of neurological and neurodegenerative diseases. One of the emerging RBPs implicated in neuronal function and neurodegeneration is splicing factor proline- and glutamine-rich (SFPQ). SFPQ is a ubiquitous and abundant RBP that plays multiple regulatory roles in the nucleus such as paraspeckle formation, DNA damage repair, and various transcriptional regulation processes. An increasing number of studies have demonstrated the nuclear and also cytoplasmic roles of SFPQ in neurons, particularly in post-transcriptional regulation and RNA granule formation. Not surprisingly, the misregulation of SFPQ has been linked to pathological features shown by other neurodegenerative disease-associated RBPs such as aberrant RNA splicing, cytoplasmic mislocalization, and aggregation. In this review, we discuss recent findings on the roles of SFPQ with a particular focus on those in neuronal development and homeostasis as well as its implications in neurodegenerative diseases.

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“…As positive controls, we used 5 pairs of RBPs that were detected in our screen and that had a least 5 independent literature sources in BioGRID confirming direct interaction (U2AF1-U2AF2; FMR1-FXR2; HNRNPK-QKI; RBFOX2-QKI; and SFPQ-NONO). In most cases, these pairs are also known to act as heterodimers and bind RNA as a complex (Fernandez et al, 2015;Li et al, 2018;Petti et al, 2019;Wu et al, 1999). As negative controls, we used randomly generated sets of RBP pairs of the same size as the screen hits.…”

Section: Direct Binary Rbp Interactions Predict Combinatorial Rna Binmentioning

confidence: 99%

rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins

Lang

Yang

Garriga-Canut

et al. 2020

Preprint

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RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory potential. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H screening to detect direct interactions between RBPs, sampling >1M possible interactions. We discovered 1994 new interactions and demonstrate that our screening detects interactions between RBPs that bind RNA in proximity. We further find that the mRNA binding region preferences of an RBP can deviate, depending on its adjacently binding interaction partner. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that RBP mutations observed in cancer rewire spliceosomal interaction networks.

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SFPQ and NONO suppress RNA:DNA-hybrid-related telomere instability

Cited by 97 publications

References 56 publications

Alternative lengthening of telomeres: from molecular mechanisms to therapeutic outlooks

Alternative lengthening of telomeres: from molecular mechanisms to therapeutic outlooks

The Emerging Role of the RNA-Binding Protein SFPQ in Neuronal Function and Neurodegeneration

rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins

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