A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells
Summary: Paraspeckles are membraneless organelles formed through liquid-liquid phase separation and consist of multiple proteins and RNAs, including NONO, SFPQ, and NEAT1. The role of paraspeckles and the component NONO in hematopoiesis remains unknown. In this study, we show histone modifier ASXL1...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472101010X |
| _version_ | 1818572799937085440 |
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| author | Keita Yamamoto Susumu Goyama Shuhei Asada Takeshi Fujino Taishi Yonezawa Naru Sato Reina Takeda Akiho Tsuchiya Tomofusa Fukuyama Yosuke Tanaka Akihiko Yokoyama Hikaru Toya Ayana Kon Yasuhito Nannya Rena Onoguchi-Mizutani Shinichi Nakagawa Tetsuro Hirose Seishi Ogawa Nobuyoshi Akimitsu Toshio Kitamura |
| author_facet | Keita Yamamoto Susumu Goyama Shuhei Asada Takeshi Fujino Taishi Yonezawa Naru Sato Reina Takeda Akiho Tsuchiya Tomofusa Fukuyama Yosuke Tanaka Akihiko Yokoyama Hikaru Toya Ayana Kon Yasuhito Nannya Rena Onoguchi-Mizutani Shinichi Nakagawa Tetsuro Hirose Seishi Ogawa Nobuyoshi Akimitsu Toshio Kitamura |
| author_sort | Keita Yamamoto |
| collection | DOAJ |
| description | Summary: Paraspeckles are membraneless organelles formed through liquid-liquid phase separation and consist of multiple proteins and RNAs, including NONO, SFPQ, and NEAT1. The role of paraspeckles and the component NONO in hematopoiesis remains unknown. In this study, we show histone modifier ASXL1 is involved in paraspeckle formation. ASXL1 forms phase-separated droplets, upregulates NEAT1 expression, and increases NONO-NEAT1 interactions through the C-terminal intrinsically disordered region (IDR). In contrast, a pathogenic ASXL mutant (ASXL1-MT) lacking IDR does not support the interaction of paraspeckle components. Furthermore, paraspeckles are disrupted and Nono localization is abnormal in the cytoplasm of hematopoietic stem and progenitor cells (HSPCs) derived from ASXL1-MT knockin mice. Nono depletion and the forced expression of cytoplasmic NONO impair the repopulating potential of HSPCs, as does ASXL1-MT. Our study indicates a link between ASXL1 and paraspeckle components in the maintenance of normal hematopoiesis. |
| first_indexed | 2024-12-15T00:02:29Z |
| format | Article |
| id | doaj.art-51f0dc93f4604f38953cd945fbc72291 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-15T00:02:29Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-51f0dc93f4604f38953cd945fbc722912022-12-21T22:42:51ZengElsevierCell Reports2211-12472021-08-01368109576A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cellsKeita Yamamoto0Susumu Goyama1Shuhei Asada2Takeshi Fujino3Taishi Yonezawa4Naru Sato5Reina Takeda6Akiho Tsuchiya7Tomofusa Fukuyama8Yosuke Tanaka9Akihiko Yokoyama10Hikaru Toya11Ayana Kon12Yasuhito Nannya13Rena Onoguchi-Mizutani14Shinichi Nakagawa15Tetsuro Hirose16Seishi Ogawa17Nobuyoshi Akimitsu18Toshio Kitamura19Division of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; The Institute of Laboratory Animals, Tokyo Women’s Medical University, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanNational Cancer Center Tsuruoka Metabolomics Laboratory, Yamagata, JapanRNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Hokkaido, JapanDepartment of Pathology and Tumor Biology, Kyoto University, Kyoto, JapanDepartment of Pathology and Tumor Biology, Kyoto University, Kyoto, JapanIsotope Science Center, The University of Tokyo, Tokyo, JapanRNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Hokkaido, JapanGraduate School of Frontier Biosciences, Osaka University, Suita, JapanDepartment of Pathology and Tumor Biology, Kyoto University, Kyoto, JapanIsotope Science Center, The University of Tokyo, Tokyo, JapanDivision of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Corresponding authorSummary: Paraspeckles are membraneless organelles formed through liquid-liquid phase separation and consist of multiple proteins and RNAs, including NONO, SFPQ, and NEAT1. The role of paraspeckles and the component NONO in hematopoiesis remains unknown. In this study, we show histone modifier ASXL1 is involved in paraspeckle formation. ASXL1 forms phase-separated droplets, upregulates NEAT1 expression, and increases NONO-NEAT1 interactions through the C-terminal intrinsically disordered region (IDR). In contrast, a pathogenic ASXL mutant (ASXL1-MT) lacking IDR does not support the interaction of paraspeckle components. Furthermore, paraspeckles are disrupted and Nono localization is abnormal in the cytoplasm of hematopoietic stem and progenitor cells (HSPCs) derived from ASXL1-MT knockin mice. Nono depletion and the forced expression of cytoplasmic NONO impair the repopulating potential of HSPCs, as does ASXL1-MT. Our study indicates a link between ASXL1 and paraspeckle components in the maintenance of normal hematopoiesis.http://www.sciencedirect.com/science/article/pii/S221112472101010XASXL1LLPSphase separationhematopoiesisHSCMDS |
| spellingShingle | Keita Yamamoto Susumu Goyama Shuhei Asada Takeshi Fujino Taishi Yonezawa Naru Sato Reina Takeda Akiho Tsuchiya Tomofusa Fukuyama Yosuke Tanaka Akihiko Yokoyama Hikaru Toya Ayana Kon Yasuhito Nannya Rena Onoguchi-Mizutani Shinichi Nakagawa Tetsuro Hirose Seishi Ogawa Nobuyoshi Akimitsu Toshio Kitamura A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells Cell Reports ASXL1 LLPS phase separation hematopoiesis HSC MDS |
| title | A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells |
| title_full | A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells |
| title_fullStr | A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells |
| title_full_unstemmed | A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells |
| title_short | A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells |
| title_sort | histone modifier asxl1 interacts with nono and is involved in paraspeckle formation in hematopoietic cells |
| topic | ASXL1 LLPS phase separation hematopoiesis HSC MDS |
| url | http://www.sciencedirect.com/science/article/pii/S221112472101010X |
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