ARC/ARG3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear speckles
Summary: ARC is a neuronal activity-induced protein interaction hub with critical roles in synaptic plasticity and memory. ARC localizes to synapses and the nucleus, but its nuclear functions are little known. Following in vivo long-term potentiation (LTP) induction in the dentate gyrus, we show tha...
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Elsevier
2025-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725002967 |
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| author | Tambudzai Kanhema Kamil Parobczak Sudarshan Patil Dagmara Holm-Kaczmarek Erik I. Hallin Jan Ludwiczak Andrzej Antoni Szczepankiewicz Francois Philippe Pauzin Aamra Mahboob Adrian Szum Yuta Ishizuka Stanisław Dunin-Horkawicz Petri Kursula Grzegorz Wilczynski Adriana Magalska Clive R. Bramham |
| author_facet | Tambudzai Kanhema Kamil Parobczak Sudarshan Patil Dagmara Holm-Kaczmarek Erik I. Hallin Jan Ludwiczak Andrzej Antoni Szczepankiewicz Francois Philippe Pauzin Aamra Mahboob Adrian Szum Yuta Ishizuka Stanisław Dunin-Horkawicz Petri Kursula Grzegorz Wilczynski Adriana Magalska Clive R. Bramham |
| author_sort | Tambudzai Kanhema |
| collection | DOAJ |
| description | Summary: ARC is a neuronal activity-induced protein interaction hub with critical roles in synaptic plasticity and memory. ARC localizes to synapses and the nucleus, but its nuclear functions are little known. Following in vivo long-term potentiation (LTP) induction in the dentate gyrus, we show that ARC accumulates in the nucleosol fraction and interchromatin space of granule cells. Proteomic analysis of immunoprecipitated ARC complexes identifies proteins involved in pre-mRNA processing. We demonstrate endogenous ARC protein-protein interaction with polyadenylate-binding nuclear protein 1 (PABPN1) and the paraspeckles protein polypyrimidine tract-binding protein (PTB)-associated splicing factor (PSF). In vitro peptide binding arrays show direct binding of purified ARC to the PABPN1 poly(A)-RNA recognition motif. 3D morphometric imaging reveals structural changes in PABPN1 foci corresponding to classical nuclear speckles following in vivo and in vitro LTP. Depletion of ARC disrupts the maintenance and activity-dependent formation of PABPN1 speckles, thus implicating ARC in regulation of nuclear speckle dynamics and pre-mRNA processing. |
| format | Article |
| id | doaj-art-18cc069a2f5446bdbdd5e8b9cfc2eeb9 |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-18cc069a2f5446bdbdd5e8b9cfc2eeb92025-08-20T03:05:21ZengElsevierCell Reports2211-12472025-04-0144411552510.1016/j.celrep.2025.115525ARC/ARG3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear specklesTambudzai Kanhema0Kamil Parobczak1Sudarshan Patil2Dagmara Holm-Kaczmarek3Erik I. Hallin4Jan Ludwiczak5Andrzej Antoni Szczepankiewicz6Francois Philippe Pauzin7Aamra Mahboob8Adrian Szum9Yuta Ishizuka10Stanisław Dunin-Horkawicz11Petri Kursula12Grzegorz Wilczynski13Adriana Magalska14Clive R. Bramham15Department of Biomedicine, University of Bergen, Bergen, Norway; Mohn Research Center for the Brain, University of Bergen, Bergen, NorwayLaboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, PolandDepartment of Biomedicine, University of Bergen, Bergen, NorwayLaboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, PolandDepartment of Biomedicine, University of Bergen, Bergen, NorwayInstitute of Evolutionary Biology, Faculty of Biology, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland; Prescient Design, Genentech Research & Early Development, Roche Group, Grenzacherstrasse 124, 4070 Basel, SwitzerlandLaboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, PolandDepartment of Biomedicine, University of Bergen, Bergen, Norway; Mohn Research Center for the Brain, University of Bergen, Bergen, NorwayDepartment of Biomedicine, University of Bergen, Bergen, Norway; Mohn Research Center for the Brain, University of Bergen, Bergen, NorwayDepartment of Biomedicine, University of Bergen, Bergen, NorwayDepartment of Biomedicine, University of Bergen, Bergen, NorwayInstitute of Evolutionary Biology, Faculty of Biology, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland; Department of Protein Evolution, Max Planck Institute for Biology Tübingen, Tübingen, GermanyDepartment of Biomedicine, University of Bergen, Bergen, Norway; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; LINXS Institute of Advanced Neutron and X-ray Science, Lund, SwedenLaboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, PolandLaboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland; Laboratory of Spatial Epigenetics, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland; Corresponding authorDepartment of Biomedicine, University of Bergen, Bergen, Norway; Mohn Research Center for the Brain, University of Bergen, Bergen, Norway; Corresponding authorSummary: ARC is a neuronal activity-induced protein interaction hub with critical roles in synaptic plasticity and memory. ARC localizes to synapses and the nucleus, but its nuclear functions are little known. Following in vivo long-term potentiation (LTP) induction in the dentate gyrus, we show that ARC accumulates in the nucleosol fraction and interchromatin space of granule cells. Proteomic analysis of immunoprecipitated ARC complexes identifies proteins involved in pre-mRNA processing. We demonstrate endogenous ARC protein-protein interaction with polyadenylate-binding nuclear protein 1 (PABPN1) and the paraspeckles protein polypyrimidine tract-binding protein (PTB)-associated splicing factor (PSF). In vitro peptide binding arrays show direct binding of purified ARC to the PABPN1 poly(A)-RNA recognition motif. 3D morphometric imaging reveals structural changes in PABPN1 foci corresponding to classical nuclear speckles following in vivo and in vitro LTP. Depletion of ARC disrupts the maintenance and activity-dependent formation of PABPN1 speckles, thus implicating ARC in regulation of nuclear speckle dynamics and pre-mRNA processing.http://www.sciencedirect.com/science/article/pii/S2211124725002967CP: Molecular biologyCP: Neuroscience |
| spellingShingle | Tambudzai Kanhema Kamil Parobczak Sudarshan Patil Dagmara Holm-Kaczmarek Erik I. Hallin Jan Ludwiczak Andrzej Antoni Szczepankiewicz Francois Philippe Pauzin Aamra Mahboob Adrian Szum Yuta Ishizuka Stanisław Dunin-Horkawicz Petri Kursula Grzegorz Wilczynski Adriana Magalska Clive R. Bramham ARC/ARG3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear speckles Cell Reports CP: Molecular biology CP: Neuroscience |
| title | ARC/ARG3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear speckles |
| title_full | ARC/ARG3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear speckles |
| title_fullStr | ARC/ARG3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear speckles |
| title_full_unstemmed | ARC/ARG3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear speckles |
| title_short | ARC/ARG3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear speckles |
| title_sort | arc arg3 1 binds the nuclear polyadenylate binding protein rrm and regulates neuronal activity dependent formation of nuclear speckles |
| topic | CP: Molecular biology CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725002967 |
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