O-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferation
Abstract Non-POU domain-containing octamer-binding protein (NONO) is a multifunctional member of the Drosophila behavior/human splicing (DBHS) protein family with DNA- and RNA-binding activity. NONO is highly expressed in various types of cancer, and excessive O-GlcNAcylation has also been implicate...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-05-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02405-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849309854833836032 |
|---|---|
| author | Yeolhoe Kim Kyung-Tae Lee Han Byeol Kim Hyeryeon Jung Jeong Yeon Ko Tae Hyun Kweon Hari Chandana Yadavalli Junghwa Seo Suena Ji Yun Ju Kim Donghyuk Shin Seong Wook Yang Myeong Min Lee Jin Won Cho Eugene C. Yi Jin-Wu Nam Won Ho Yang |
| author_facet | Yeolhoe Kim Kyung-Tae Lee Han Byeol Kim Hyeryeon Jung Jeong Yeon Ko Tae Hyun Kweon Hari Chandana Yadavalli Junghwa Seo Suena Ji Yun Ju Kim Donghyuk Shin Seong Wook Yang Myeong Min Lee Jin Won Cho Eugene C. Yi Jin-Wu Nam Won Ho Yang |
| author_sort | Yeolhoe Kim |
| collection | DOAJ |
| description | Abstract Non-POU domain-containing octamer-binding protein (NONO) is a multifunctional member of the Drosophila behavior/human splicing (DBHS) protein family with DNA- and RNA-binding activity. NONO is highly expressed in various types of cancer, and excessive O-GlcNAcylation has also been implicated in tumorigenesis. Although recent studies revealed that NONO is O-GlcNAcylated and that this modification is involved in DNA damage repair, it remains unknown whether O-GlcNAcylation of NONO regulates cancer cell proliferation. Additionally, little is known about the effect of O-GlcNAcylation on other biological properties of NONO. In this study, we identify Thr440 as the primary NONO O-GlcNAcylation site and demonstrates its crucial role in the assembly of paraspeckles, an important subnuclear compartment that facilitates NONO-dependent transcriptional regulation in mammalian cells. Moreover, we found that O-GlcNAcylation of NONO is required to maintain the expression of genes related to microtubule cytoskeleton organization involved in mitosis and to suppress the expression of genes related to cellular response to type I interferon. Regarding the regulation of these genes, depletion of NONO O-GlcNAcylation at Thr440 significantly inhibited the proliferation of colon cancer cells. Collectively, our findings highlight NONO O-GlcNAcylation as a key regulator modulating paraspeckle formation and as a candidate therapeutic target in colon cancer. |
| format | Article |
| id | doaj-art-0412cbe7d70e4aeca7c058b8ccdbb245 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-0412cbe7d70e4aeca7c058b8ccdbb2452025-08-20T03:53:57ZengNature Publishing GroupCell Death Discovery2058-77162025-05-0111111210.1038/s41420-025-02405-zO-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferationYeolhoe Kim0Kyung-Tae Lee1Han Byeol Kim2Hyeryeon Jung3Jeong Yeon Ko4Tae Hyun Kweon5Hari Chandana Yadavalli6Junghwa Seo7Suena Ji8Yun Ju Kim9Donghyuk Shin10Seong Wook Yang11Myeong Min Lee12Jin Won Cho13Eugene C. Yi14Jin-Wu Nam15Won Ho Yang16Department of Systems Biology, College of Life Science and Biotechnology, Yonsei UniversityDepartment of Life Sciences, College of Natural Science, Hanyang UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National UniversityDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei UniversityDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei UniversityDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei UniversityGlycosylation Network Research Center, Yonsei UniversityGlycosylation Network Research Center, Yonsei UniversityDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei UniversityDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei UniversityDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei UniversityDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei UniversityGlycosylation Network Research Center, Yonsei UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National UniversityDepartment of Life Sciences, College of Natural Science, Hanyang UniversityDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei UniversityAbstract Non-POU domain-containing octamer-binding protein (NONO) is a multifunctional member of the Drosophila behavior/human splicing (DBHS) protein family with DNA- and RNA-binding activity. NONO is highly expressed in various types of cancer, and excessive O-GlcNAcylation has also been implicated in tumorigenesis. Although recent studies revealed that NONO is O-GlcNAcylated and that this modification is involved in DNA damage repair, it remains unknown whether O-GlcNAcylation of NONO regulates cancer cell proliferation. Additionally, little is known about the effect of O-GlcNAcylation on other biological properties of NONO. In this study, we identify Thr440 as the primary NONO O-GlcNAcylation site and demonstrates its crucial role in the assembly of paraspeckles, an important subnuclear compartment that facilitates NONO-dependent transcriptional regulation in mammalian cells. Moreover, we found that O-GlcNAcylation of NONO is required to maintain the expression of genes related to microtubule cytoskeleton organization involved in mitosis and to suppress the expression of genes related to cellular response to type I interferon. Regarding the regulation of these genes, depletion of NONO O-GlcNAcylation at Thr440 significantly inhibited the proliferation of colon cancer cells. Collectively, our findings highlight NONO O-GlcNAcylation as a key regulator modulating paraspeckle formation and as a candidate therapeutic target in colon cancer.https://doi.org/10.1038/s41420-025-02405-z |
| spellingShingle | Yeolhoe Kim Kyung-Tae Lee Han Byeol Kim Hyeryeon Jung Jeong Yeon Ko Tae Hyun Kweon Hari Chandana Yadavalli Junghwa Seo Suena Ji Yun Ju Kim Donghyuk Shin Seong Wook Yang Myeong Min Lee Jin Won Cho Eugene C. Yi Jin-Wu Nam Won Ho Yang O-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferation Cell Death Discovery |
| title | O-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferation |
| title_full | O-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferation |
| title_fullStr | O-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferation |
| title_full_unstemmed | O-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferation |
| title_short | O-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferation |
| title_sort | o glcnacylation of nono regulates paraspeckle component assembly and contributes to colon cancer cell proliferation |
| url | https://doi.org/10.1038/s41420-025-02405-z |
| work_keys_str_mv | AT yeolhoekim oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT kyungtaelee oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT hanbyeolkim oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT hyeryeonjung oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT jeongyeonko oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT taehyunkweon oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT harichandanayadavalli oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT junghwaseo oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT suenaji oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT yunjukim oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT donghyukshin oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT seongwookyang oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT myeongminlee oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT jinwoncho oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT eugenecyi oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT jinwunam oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation AT wonhoyang oglcnacylationofnonoregulatesparaspecklecomponentassemblyandcontributestocoloncancercellproliferation |