The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the <i>MT-ND3</i> mRNA

Article Article scientifique Article The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the <i>MT-ND3</i> mRNA eng 2024-12-27 author Yang Xuan 847783 author Stentenbach Maike author Hughes Laetitia A author Siira Stefan J author Lau Kelvin Ka Ching 0000-0002-9040-7597 831683 Kelvin Lau author Hothorn Michael 0000-0002-3597-5698 826130 Département des sciences végétales (BIVEG) author Martinou Jean-Claude 27293 Département de biologie moléculaire et cellulaire (MOCEL) author Rackham Oliver author Filipovska Aleksandra 0000-0002-6998-8403 gkae1261 10.1093/nar/gkae1261 0305-1048 https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkae1261/7933595 Expression of the compact mitochondrial genome is regulated by nuclear encoded, mitochondrially localized RNA-binding proteins (RBPs). RBPs regulate the lifecycles of mitochondrial RNAs from transcription to degradation by mediating RNA processing, maturation, stability and translation. The Fas-activated serine/threonine kinase (FASTK) family of RBPs has been shown to regulate and fine-tune discrete aspects of mitochondrial gene expression. Although the roles of specific targets of FASTK proteins have been elucidated, the molecular mechanisms of FASTK proteins in mitochondrial RNA metabolism remain unclear. Therefore, we resolved the structure of FASTKD4 at atomic level that includes the RAP domain and the two FAST motifs, creating a positively charged cavity resembling that of the very short patch repair endonuclease. Our biochemical studies show that FASTKD4 binds the canonical poly(A) tail of MT-ND3 enabling its maturation and translation. The in vitro role of FASTKD4 is consistent with its loss in cells that results in decreased MT-ND3 polyadenylation, which destabilizes this messenger RNA in mitochondria. Dewey 580 Dewey 570 National Health and Medical Research Council GNT1058442 Australian Research Council DP180101656 45 Département des sciences végétales 163 7daed2ee-1311-4824-9df9-2e51260a966a Département de biologie moléculaire et cellulaire 16484 false 830 Groupe Hothorn Nucleic acids research 53 3dc4673e-e0a1-428c-b5f8-ff2a9c1f6e28 Article (Published version) Public gkae1261.pdf 2257617 application/pdf CC BY-4.0 e80e5ca5a74587e5311a7a8cc9a66447bfc09158a5e2f5f1ef387430f7afec4e openAccess Faculté des sciences / Section de biologie / Département des sciences végétales Faculté des sciences / Section de biologie / Département de biologie moléculaire et cellulaire

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The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the MT-ND3 mRNA	Nucleic acids research			2024	44	30

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Yang, Xuan