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Heterogeneous nuclear ribonucleoprotein A1 post-transcriptionally regulates Drp1 expression in neuroblastoma cells.


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Authors

Park, So Jung 
Lee, Heejin 
Jo, Doo Shin 
Jo, Yoon Kyung 
Shin, Ji Hyun 

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.

Description

Keywords

Drp1, Mitochondria dynamics, RNA binding protein, hnRNP A1, 3' Untranslated Regions, Cell Line, Tumor, Cell Nucleus, Cytoplasm, Dynamins, GTP Phosphohydrolases, Gene Expression Regulation, Neoplastic, Heterogeneous Nuclear Ribonucleoprotein A1, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, Microtubule-Associated Proteins, Mitochondrial Dynamics, Mitochondrial Proteins, Neoplasm Proteins, Neuroblastoma, Protein Binding, Protein Transport, RNA Processing, Post-Transcriptional, RNA, Messenger, RNA, Neoplasm

Journal Title

Biochim Biophys Acta

Conference Name

Journal ISSN

0006-3002
1876-4320

Volume Title

1849

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (095317/Z/11/A)
Wellcome Trust (095317/Z/11/Z)
Wellcome Trust (100140/Z/12/Z)
This research was supported by a grant of the Korea–UK Collaborative Alzheimer's Disease Research Project by Ministry of Health & Welfare, Republic of Korea (A120196, HI14C1913) and was supported by the Basic Science Research Program of the National Research Foundation, Republic of Korea (2014R1A2A1A11053431). We are grateful to Wellcome Trust, Principal Research Fellowship to DCR (095317/Z/11/Z)