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NF90 interacts with components of RISC and modulates association of Ago2 with mRNA

BACKGROUND: Nuclear factor 90 (NF90) is a double-stranded RNA-binding protein involved in a multitude of different cellular mechanisms such as transcription, translation, viral infection, and mRNA stability. Recent data suggest that NF90 might influence the abundance of target mRNAs in the cytoplasm...

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Autores principales: Grasso, Giuseppa, Akkawi, Charbel, Franckhauser, Celine, Nait-Saidi, Rima, Bello, Maxime, Barbier, Jérôme, Kiernan, Rosemary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438302/
https://www.ncbi.nlm.nih.gov/pubmed/36050755
http://dx.doi.org/10.1186/s12915-022-01384-2
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author Grasso, Giuseppa
Akkawi, Charbel
Franckhauser, Celine
Nait-Saidi, Rima
Bello, Maxime
Barbier, Jérôme
Kiernan, Rosemary
author_facet Grasso, Giuseppa
Akkawi, Charbel
Franckhauser, Celine
Nait-Saidi, Rima
Bello, Maxime
Barbier, Jérôme
Kiernan, Rosemary
author_sort Grasso, Giuseppa
collection PubMed
description BACKGROUND: Nuclear factor 90 (NF90) is a double-stranded RNA-binding protein involved in a multitude of different cellular mechanisms such as transcription, translation, viral infection, and mRNA stability. Recent data suggest that NF90 might influence the abundance of target mRNAs in the cytoplasm through miRNA- and Argonaute 2 (Ago2)-dependent activity. RESULTS: Here, we identified the interactome of NF90 in the cytoplasm, which revealed several components of the RNA-induced silencing complex (RISC) and associated factors. Co-immunoprecipitation analysis confirmed the interaction of NF90 with the RISC-associated RNA helicase, Moloney leukemia virus 10 (MOV10), and other proteins involved in RISC-mediated silencing, including Ago2. Furthermore, NF90 association with MOV10 and Ago2 was found to be RNA-dependent. Glycerol gradient sedimentation of NF90 immune complexes indicates that these proteins occur in the same protein complex. At target RNAs predicted to bind both NF90 and MOV10 in their 3′ UTRs, NF90 association was increased upon loss of MOV10 and vice versa. Interestingly, loss of NF90 led to an increase in association of Ago2 as well as a decrease in the abundance of the target mRNA. Similarly, during hypoxia, the binding of Ago2 to vascular endothelial growth factor (VEGF) mRNA increased after loss of NF90, while the level of VEGF mRNA decreased. CONCLUSIONS: These findings reveal that, in the cytoplasm, NF90 can associate with components of RISC such as Ago2 and MOV10. In addition, the data indicate that NF90 and MOV10 may compete for the binding of common target mRNAs, suggesting a role for NF90 in the regulation of RISC-mediated silencing by stabilizing target mRNAs, such as VEGF, during cancer-induced hypoxia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-022-01384-2.
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spelling pubmed-94383022022-09-03 NF90 interacts with components of RISC and modulates association of Ago2 with mRNA Grasso, Giuseppa Akkawi, Charbel Franckhauser, Celine Nait-Saidi, Rima Bello, Maxime Barbier, Jérôme Kiernan, Rosemary BMC Biol Research Article BACKGROUND: Nuclear factor 90 (NF90) is a double-stranded RNA-binding protein involved in a multitude of different cellular mechanisms such as transcription, translation, viral infection, and mRNA stability. Recent data suggest that NF90 might influence the abundance of target mRNAs in the cytoplasm through miRNA- and Argonaute 2 (Ago2)-dependent activity. RESULTS: Here, we identified the interactome of NF90 in the cytoplasm, which revealed several components of the RNA-induced silencing complex (RISC) and associated factors. Co-immunoprecipitation analysis confirmed the interaction of NF90 with the RISC-associated RNA helicase, Moloney leukemia virus 10 (MOV10), and other proteins involved in RISC-mediated silencing, including Ago2. Furthermore, NF90 association with MOV10 and Ago2 was found to be RNA-dependent. Glycerol gradient sedimentation of NF90 immune complexes indicates that these proteins occur in the same protein complex. At target RNAs predicted to bind both NF90 and MOV10 in their 3′ UTRs, NF90 association was increased upon loss of MOV10 and vice versa. Interestingly, loss of NF90 led to an increase in association of Ago2 as well as a decrease in the abundance of the target mRNA. Similarly, during hypoxia, the binding of Ago2 to vascular endothelial growth factor (VEGF) mRNA increased after loss of NF90, while the level of VEGF mRNA decreased. CONCLUSIONS: These findings reveal that, in the cytoplasm, NF90 can associate with components of RISC such as Ago2 and MOV10. In addition, the data indicate that NF90 and MOV10 may compete for the binding of common target mRNAs, suggesting a role for NF90 in the regulation of RISC-mediated silencing by stabilizing target mRNAs, such as VEGF, during cancer-induced hypoxia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-022-01384-2. BioMed Central 2022-09-01 /pmc/articles/PMC9438302/ /pubmed/36050755 http://dx.doi.org/10.1186/s12915-022-01384-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Grasso, Giuseppa
Akkawi, Charbel
Franckhauser, Celine
Nait-Saidi, Rima
Bello, Maxime
Barbier, Jérôme
Kiernan, Rosemary
NF90 interacts with components of RISC and modulates association of Ago2 with mRNA
title NF90 interacts with components of RISC and modulates association of Ago2 with mRNA
title_full NF90 interacts with components of RISC and modulates association of Ago2 with mRNA
title_fullStr NF90 interacts with components of RISC and modulates association of Ago2 with mRNA
title_full_unstemmed NF90 interacts with components of RISC and modulates association of Ago2 with mRNA
title_short NF90 interacts with components of RISC and modulates association of Ago2 with mRNA
title_sort nf90 interacts with components of risc and modulates association of ago2 with mrna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438302/
https://www.ncbi.nlm.nih.gov/pubmed/36050755
http://dx.doi.org/10.1186/s12915-022-01384-2
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