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ATP regulates RNA‐driven cold inducible RNA binding protein phase separation
Intrinsically disordered proteins and proteins containing intrinsically disordered regions are highly abundant in the proteome of eukaryotes and are extensively involved in essential biological functions. More recently, their role in the organization of biomolecular condensates has become evident an...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197425/ https://www.ncbi.nlm.nih.gov/pubmed/33991007 http://dx.doi.org/10.1002/pro.4123 |
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author | Zhou, Qishun Usluer, Sinem Zhang, Fangrong Lenard, Aneta J. Bourgeois, Benjamin M. R. Madl, Tobias |
author_facet | Zhou, Qishun Usluer, Sinem Zhang, Fangrong Lenard, Aneta J. Bourgeois, Benjamin M. R. Madl, Tobias |
author_sort | Zhou, Qishun |
collection | PubMed |
description | Intrinsically disordered proteins and proteins containing intrinsically disordered regions are highly abundant in the proteome of eukaryotes and are extensively involved in essential biological functions. More recently, their role in the organization of biomolecular condensates has become evident and along with their misregulation in several neurologic disorders. Currently, most studies involving these proteins are carried out in vitro and using purified proteins. Given that in cells, condensate‐forming proteins are exposed to high, millimolar concentrations of cellular metabolites, we aimed to reveal the interactions of cellular metabolites and a representative condensate‐forming protein. Here, using the arginine–glycine/arginine–glycine–glycine (RG/RGG)‐rich cold inducible RNA binding protein (CIRBP) as paradigm, we studied binding of the cellular metabolome to CIRBP. We found that most of the highly abundant cellular metabolites, except nucleotides, do not directly bind to CIRBP. ATP, ADP, and AMP as well as NAD(+), NADH, NADP(+), and NADPH directly interact with CIRBP, involving both the folded RNA‐recognition motif and the disordered RG/RGG region. ATP binding inhibited RNA‐driven phase separation of CIRBP. Thus, it might be beneficial to include cellular metabolites in in vitro liquid–liquid phase separation studies of RG/RGG and other condensate‐forming proteins in order to better mimic the cellular environment in the future. |
format | Online Article Text |
id | pubmed-8197425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81974252021-06-15 ATP regulates RNA‐driven cold inducible RNA binding protein phase separation Zhou, Qishun Usluer, Sinem Zhang, Fangrong Lenard, Aneta J. Bourgeois, Benjamin M. R. Madl, Tobias Protein Sci Full‐Length Papers Intrinsically disordered proteins and proteins containing intrinsically disordered regions are highly abundant in the proteome of eukaryotes and are extensively involved in essential biological functions. More recently, their role in the organization of biomolecular condensates has become evident and along with their misregulation in several neurologic disorders. Currently, most studies involving these proteins are carried out in vitro and using purified proteins. Given that in cells, condensate‐forming proteins are exposed to high, millimolar concentrations of cellular metabolites, we aimed to reveal the interactions of cellular metabolites and a representative condensate‐forming protein. Here, using the arginine–glycine/arginine–glycine–glycine (RG/RGG)‐rich cold inducible RNA binding protein (CIRBP) as paradigm, we studied binding of the cellular metabolome to CIRBP. We found that most of the highly abundant cellular metabolites, except nucleotides, do not directly bind to CIRBP. ATP, ADP, and AMP as well as NAD(+), NADH, NADP(+), and NADPH directly interact with CIRBP, involving both the folded RNA‐recognition motif and the disordered RG/RGG region. ATP binding inhibited RNA‐driven phase separation of CIRBP. Thus, it might be beneficial to include cellular metabolites in in vitro liquid–liquid phase separation studies of RG/RGG and other condensate‐forming proteins in order to better mimic the cellular environment in the future. John Wiley & Sons, Inc. 2021-05-22 2021-07 /pmc/articles/PMC8197425/ /pubmed/33991007 http://dx.doi.org/10.1002/pro.4123 Text en © 2021 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full‐Length Papers Zhou, Qishun Usluer, Sinem Zhang, Fangrong Lenard, Aneta J. Bourgeois, Benjamin M. R. Madl, Tobias ATP regulates RNA‐driven cold inducible RNA binding protein phase separation |
title | ATP regulates RNA‐driven cold inducible RNA binding protein phase separation |
title_full | ATP regulates RNA‐driven cold inducible RNA binding protein phase separation |
title_fullStr | ATP regulates RNA‐driven cold inducible RNA binding protein phase separation |
title_full_unstemmed | ATP regulates RNA‐driven cold inducible RNA binding protein phase separation |
title_short | ATP regulates RNA‐driven cold inducible RNA binding protein phase separation |
title_sort | atp regulates rna‐driven cold inducible rna binding protein phase separation |
topic | Full‐Length Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197425/ https://www.ncbi.nlm.nih.gov/pubmed/33991007 http://dx.doi.org/10.1002/pro.4123 |
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