title: Heterogeneous nuclear ribonucleoprotein A1 post-transcriptionally regulates Drp1 expression in neuroblastoma cells.
abstract: Excessive mitochondrial fission is associated with the pathogenesis of neurodegenerative diseases. Dynamin-related protein 1 (Drp1) possesses specific fission activity in the mitochondria and peroxisomes. Various post-translational modifications of Drp1 are known to modulate complex mitochondrial dynamics. However, the post-transcriptional regulation of Drp1 remains poorly understood. Here, we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) regulates Drp1 expression at the post-transcriptional level. hnRNP A1 directly interacts with Drp1 mRNA at its 3'UTR region, and enhances translation potential without affecting mRNA stability. Down-regulation of hnRNP A1 induces mitochondrial elongation by reducing Drp1 expression. Moreover, depletion of hnRNP A1 suppresses 3-NP-mediated mitochondrial fission and dysfunction. In contrast, over-expression of hnRNP A1 promotes mitochondrial fragmentation by increasing Drp1 expression. Additionally, hnRNP A1 significantly exacerbates 3-NP-induced mitochondrial dysfunction and cell death in neuroblastoma cells. Interestingly, treatment with 3-NP induces subcellular translocation of hnRNP A1 from the nucleus to the cytoplasm, which accelerates the increase in Drp1 expression in hnRNP A1 over-expressing cells. Collectively, our findings suggest that hnRNP A1 controls mitochondrial dynamics by post-transcriptional regulation of Drp1.
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Heejin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Doo Shin
authors.initials: DS
authors.lastname: Jo
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jo
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Han Byeol
authors.initials: HB
authors.lastname: Kim
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Hae Mi
authors.initials: HM
authors.lastname: Seo
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
authors.affiliation: Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Koh
authors.affiliation: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address: leeek@catholic.ac.kr.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea. Electronic address: dhcho@khu.ac.kr.
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D063154:Mitochondrial Dynamics / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000619656:hnRNPA1 protein, human; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins
keywords: Drp1; Mitochondria dynamics; RNA binding protein; hnRNP A1