Title: Identification and characterization of a special type of subnuclear structure: AGGF1‐coated paraspeckles
Abstract: The FASEB JournalVolume 36, Issue 6 e22366 RESEARCH ARTICLE Identification and characterization of a special type of subnuclear structure: AGGF1-coated paraspeckles Jinyan Zhao, Jinyan Zhao orcid.org/0000-0002-8125-0516 Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorWen Xie, Wen Xie Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorZhongcheng Yang, Zhongcheng Yang Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorMiao Zhao, Miao Zhao Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorTie Ke, Tie Ke Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorChengqi Xu, Chengqi Xu Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorHui Li, Hui Li Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorQiuyun Chen, Corresponding Author Qiuyun Chen [email protected] Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA Correspondence Qiuyun Chen, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Email: [email protected] Qing K. Wang, Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China. Email: [email protected] for more papers by this authorQing K. Wang, Corresponding Author Qing K. Wang [email protected] orcid.org/0000-0002-2235-6572 Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China Correspondence Qiuyun Chen, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Email: [email protected] Qing K. Wang, Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China. Email: [email protected] for more papers by this author Jinyan Zhao, Jinyan Zhao orcid.org/0000-0002-8125-0516 Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorWen Xie, Wen Xie Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorZhongcheng Yang, Zhongcheng Yang Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorMiao Zhao, Miao Zhao Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorTie Ke, Tie Ke Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorChengqi Xu, Chengqi Xu Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorHui Li, Hui Li Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. ChinaSearch for more papers by this authorQiuyun Chen, Corresponding Author Qiuyun Chen [email protected] Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA Correspondence Qiuyun Chen, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Email: [email protected] Qing K. Wang, Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China. Email: [email protected] for more papers by this authorQing K. Wang, Corresponding Author Qing K. Wang [email protected] orcid.org/0000-0002-2235-6572 Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China Correspondence Qiuyun Chen, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Email: [email protected] Qing K. Wang, Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China. Email: [email protected] for more papers by this author First published: 24 May 2022 https://doi.org/10.1096/fj.202101690RR Jinyan Zhao, Wen Xie and Zhongcheng Yang are co-first authors. Chengqi Xu, Hui Li, Qiuyun Chen and Qing K. Wang contributed equally to this study. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract AGGF1 is an angiogenic factor with G-Patch and FHA domains 1 described by our group. Gain-of-function mutations in AGGF1 cause Klippel–Trenaunay syndrome, whereas somatic loss-of-function mutations cause cancer. Paraspeckles are small membraneless subnuclear structures with a diameter of 0.5–1 μm, and composed of lncRNA NEAT1 as the scaffold and three core RNA-binding proteins NONO, PSPC1, and PSF. Here, we show that AGGF1 is a key regulatory and structural component of paraspeckles that induces paraspeckle formation, forms an outside rim of paraspeckles, wraps around the NONO/PSF/PSPC1/NEAT1 core, and regulates the size and number of paraspeckles. AGGF1-paraspeckles are larger (>1 μm) than conventional paraspeckles. RNA-FISH in combination with immunostaining shows that AGGF1, NONO, and NEAT1_2 co-localize in 20.58% of NEAT1_2-positive paraspeckles. Mechanistically, AGGF1 interacts with NONO, PSF, and HNRNPK, and upregulates NEAT1_2, a longer, 23 kb NEAT1 transcript with a key role in regulation of paraspeckle size and number. RNA-immunoprecipitation shows that AGGF1 interacts with NEAT1, which may be another possible mechanism underlying the formation of AGGF1-paraspeckles. NEAT1_2 knockdown reduces the number and size of AGGF1-paraspeckles. Functionally, AGGF1 regulates alternative RNA splicing as it decreases the exon skipping/inclusion ratio in a CD44 model. AGGF1 is also localized in some nuclear foci without NEAT1 or NONO, suggesting that AGGF1 is an important liquid–liquid phase separation (LLPS) driver for other types of AGGF1-positive nuclear condensates (referred to as AGGF1-bodies). Our results identify a special type of AGGF1-coated paraspeckles and provide important insights into the formation, structure, and function of paraspeckles. Open Research DATA AVAILABILITY STATEMENT The data that support the findings of this study are available in the results and Supporting Information of this article. Supporting Information Filename Description fsb222366-sup-0001-TextS1.docxWord 2007 document , 5.3 MB Text S1 fsb222366-sup-0002-VideoS1.wmvvideo/wmv, 64.5 KB Video S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume36, Issue6June 2022e22366 RelatedInformation
Publication Year: 2022
Publication Date: 2022-05-24
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
Access and Citation
Cited By Count: 5
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot