A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells

被引：21

作者：

Yamamoto, Keita ^{[1
]}

Goyama, Susumu ^{[1
]}

Asada, Shuhei ^{[1
,2
]}

Fujino, Takeshi ^{[1
]}

Yonezawa, Taishi ^{[1
]}

Sato, Naru ^{[1
]}

Takeda, Reina ^{[1
]}

Tsuchiya, Akiho ^{[1
]}

Fukuyama, Tomofusa ^{[1
]}

Tanaka, Yosuke ^{[1
]}

Yokoyama, Akihiko ^{[3
]}

Toya, Hikaru ^{[4
]}

Kon, Ayana ^{[5
]}

Nannya, Yasuhito ^{[5
]}

Onoguchi-Mizutani, Rena ^{[6
]}

Nakagawa, Shinichi ^{[4
]}

Hirose, Tetsuro ^{[7
]}

Ogawa, Seishi ^{[5
]}

Akimitsu, Nobuyoshi ^{[6
]}

Kitamura, Toshio ^{[1
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Div Cellular Therapy, Tokyo, Japan

[2] Tokyo Womens Med Univ, Inst Lab Anim, Tokyo, Japan

[3] Natl Canc Ctr, Tsuruoka Metabol Lab, Yamagata, Japan

[4] Hokkaido Univ, Fac Pharmaceut Sci, RNA Biol Lab, Sapporo, Hokkaido, Japan

[5] Kyoto Univ, Dept Pathol & Tumor Biol, Kyoto, Japan

[6] Univ Tokyo, Isotope Sci Ctr, Tokyo, Japan

[7] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka, Japan

来源：

CELL REPORTS | 2021年 / 36卷 / 08期

基金：

日本学术振兴会;

关键词：

LONG NONCODING RNA; MYELODYSPLASTIC SYNDROMES; PROTEIN; GENE; EXPRESSION; NEAT1; POLYCOMB; TRANSFORMATION; EPIGENETICS; STABILITY;

D O I：

10.1016/j.celrep.2021.109576

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 ASXL1MT. Our study indicates a link between ASXL1 and paraspeckle components in the maintenance of normal hematopoiesis.

引用

页数：26

共 31 条

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CELL DISCOVERY, 2018, 4
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PLOS ONE, 2016, 11 (10):
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