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The effects of NCBP3 on METTL3-mediated m6A RNA methylation to enhance translation process in hypoxic cardiomyocytes.
Ye, Fei; Wang, Xiaoyan; Tu, San; Zeng, Lixiong; Deng, Xu; Luo, Wenzhi; Zhang, Zhihui.
Afiliación
  • Ye F; Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, China.
  • Wang X; Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, China.
  • Tu S; Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, China.
  • Zeng L; Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, China.
  • Deng X; Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, China.
  • Luo W; Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, China.
  • Zhang Z; Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, China.
J Cell Mol Med ; 25(18): 8920-8928, 2021 09.
Article en En | MEDLINE | ID: mdl-34382339
Hypoxia as a crucial pathogenesis factor usually results in huge harmful effects on cardiac injury and dysfunction. Our previous study has uncovered the global transcriptome and translatome profiles of cardiomyocytes in vitro and in vivo to response to hypoxia by RNA sequencing and ribosome profiling sequencing. We observe a series of differential expressed genes between transcription and translation, which may be attributed to the hypoxia-specific binding affinity of nuclear cap-binding subunit 3 (NCBP3) at 5' untranslation region of target genes. Although we observe that NCBP3 can facilitate translational process in myocardium under hypoxia stress, the underlying molecular mechanism of NCBP3 for gene translation modulation remains unclear. In this study, we performed NCBP3 immunoprecipitation for mass spectrum and found that METTL3 and eIF4A2 particularly interacted with NCBP3 in hypoxic rat H9C2 cardiomyocytes. Furthermore, we observed that METTL3-mediated N6-methyladenosine (m6A) methylation was elevated in hypoxia, but compromised by NCBP3 or METTL3 knockdown. Finally, we also demonstrated that NCBP3/METTL3/eIF4A2 regulatory axis plays a specific role in cardiomyocytes undergoing hypoxic stress. Taken together, we unmasked NCBP3, a novel hypoxia-specific response protein functions as a scaffold to coordinate METTL3 and eIF4A2 for enhancing gene translation by m6A RNA methylation in cardiomyocytes upon hypoxic stress.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Mensajero / Hipoxia de la Célula / Complejo Proteico Nuclear de Unión a la Caperuza / Metiltransferasas Límite: Animals Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Mensajero / Hipoxia de la Célula / Complejo Proteico Nuclear de Unión a la Caperuza / Metiltransferasas Límite: Animals Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido