PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA

Uozumi, Ryota; Mori, Kohji; Gotoh, Shiho; Miyamoto, Tesshin; Kondo, Shizuko; Yamashita, Tomoko; Kawabe, Yuya; Tagami, Shinji; Akamine, Shoshin; Ikeda, Manabu

doi:https://doi.org/10.1016/j.isci.2024.109303

PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA

Uozumi, Ryota; Mori, Kohji; Gotoh, Shiho et al.

iScience, 2024, 27(3), 109303

アクセス数:1,406件（2026-04-06 06:37 集計）

固定URL: https://hdl.handle.net/11094/94894

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タイトル	PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA
著者	著者名 Uozumi, Ryota
	NRID 1000040775318 1000040775318 ORCID 0000-0003-2629-0723 0000-0003-2629-0723 researchmap permalink kmori_psy kmori_psy Scopus Author ID 55579363000 55579363000 著者名 Mori, Kohji
	著者名 Gotoh, Shiho
	著者名 Miyamoto, Tesshin
	著者名 Kondo, Shizuko
	著者名 Yamashita, Tomoko
	著者名 Kawabe, Yuya
	NRID 1000040362735 1000040362735 著者名 Tagami, Shinji
	NRID 1000000846222 1000000846222 ORCID 0000-0001-6476-6222 0000-0001-6476-6222 researchmap permalink shak shak Scopus Author ID 57219991127 57219991127 著者名 Akamine, Shoshin
	NRID 1000060284395 1000060284395 researchmap permalink manabu_ikeda manabu_ikeda Scopus Author ID 7404692889 7404692889 著者名 Ikeda, Manabu
キーワード等	Biomolecules
	Molecular interaction
	Properties of biomolecules
内容	Uozumi R., Mori K., Gotoh S., et al. PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA. iScience 27, 109303 (2024); https://doi.org/10.1016/j.isci.2024.109303.
抄録	GGGGCC hexanucleotide repeat expansion in C9orf72 causes frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Expanded GGGGCC repeat RNA accumulates within RNA foci and is translated into toxic dipeptide repeat proteins; thus, efficient repeat RNA degradation may alleviate diseases. hnRNPA3, one of the repeat RNA-binding proteins, has been implicated in the destabilization of repeat RNA. Using APEX2-mediated proximity biotinylation, here, we demonstrate PABPC1, a cytoplasmic poly (A)-binding protein, interacts with hnRNPA3. Knockdown of PABPC1 increased the accumulation of repeat RNA and RNA foci to the same extent as the knockdown of hnRNPA3. Proximity ligation assays indicated PABPC1-hnRNPA3 and PABPC1-RNA exosomes, a complex that degrades repeat RNA, preferentially co-localized when repeat RNA was present. Our results suggest that PABPC1 functions as a mediator of polyadenylated GGGGCC repeat RNA degradation through interactions with hnRNPA3 and RNA exosome complex.
出版者	Elsevier Inc.
収録物名	iScience
巻(号)	27(3)
ページ	109303
刊行年月	2024-03-15
言語	英語
ハンドルURL	https://hdl.handle.net/11094/94894
eISSN	25890042
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.isci.2024.109303
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	iScience. 2024, 27(3), p. 109303
DC.title	PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA
DC.creator	Uozumi, Ryota
	Mori, Kohji
	Gotoh, Shiho
	Miyamoto, Tesshin
	Kondo, Shizuko
	Yamashita, Tomoko
	Kawabe, Yuya
	Tagami, Shinji
	Akamine, Shoshin
	Ikeda, Manabu
DC.publisher	Elsevier Inc.
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-03-15
DC.identifier	https://doi.org/10.1016/j.isci.2024.109303
DC.subject	Biomolecules
	Molecular interaction
	Properties of biomolecules
DC.description	Uozumi R., Mori K., Gotoh S., et al. PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA. iScience 27, 109303 (2024); https://doi.org/10.1016/j.isci.2024.109303.
DCTERMS.abstract	GGGGCC hexanucleotide repeat expansion in C9orf72 causes frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Expanded GGGGCC repeat RNA accumulates within RNA foci and is translated into toxic dipeptide repeat proteins; thus, efficient repeat RNA degradation may alleviate diseases. hnRNPA3, one of the repeat RNA-binding proteins, has been implicated in the destabilization of repeat RNA. Using APEX2-mediated proximity biotinylation, here, we demonstrate PABPC1, a cytoplasmic poly (A)-binding protein, interacts with hnRNPA3. Knockdown of PABPC1 increased the accumulation of repeat RNA and RNA foci to the same extent as the knockdown of hnRNPA3. Proximity ligation assays indicated PABPC1-hnRNPA3 and PABPC1-RNA exosomes, a complex that degrades repeat RNA, preferentially co-localized when repeat RNA was present. Our results suggest that PABPC1 functions as a mediator of polyadenylated GGGGCC repeat RNA degradation through interactions with hnRNPA3 and RNA exosome complex.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	94894
citation_title	PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA
citation_author	Uozumi, Ryota
	Mori, Kohji
	Gotoh, Shiho
	Miyamoto, Tesshin
	Kondo, Shizuko
	Yamashita, Tomoko
	Kawabe, Yuya
	Tagami, Shinji
	Akamine, Shoshin
	Ikeda, Manabu
citation_publisher	Elsevier Inc.
citation_language	英語
citation_date	2024-03-15
citation_journal_title	iScience
citation_volume	27
citation_issue	3
citation_firstpage	109303
citation_doi	https://doi.org/10.1016/j.isci.2024.109303
citation_public_url	https://hdl.handle.net/11094/94894

PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA

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