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Full-Text Articles in Medicine and Health Sciences
Recognition Of The Tdp-43 Nuclear Localization Signal By Importin Α1/Β, Steven G Doll, Hamed Meshkin, Alexander J Bryer, Fenglin Li, Ying-Hui Ko, Ravi K Lokareddy, Richard E Gillilan, Kushol Gupta, Juan R Perilla, Gino Cingolani
Recognition Of The Tdp-43 Nuclear Localization Signal By Importin Α1/Β, Steven G Doll, Hamed Meshkin, Alexander J Bryer, Fenglin Li, Ying-Hui Ko, Ravi K Lokareddy, Richard E Gillilan, Kushol Gupta, Juan R Perilla, Gino Cingolani
Department of Biochemistry and Molecular Biology Faculty Papers
Cytoplasmic mislocalization of the TAR-DNA binding protein of 43 kDa (TDP-43) leads to large, insoluble aggregates that are a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. Here, we study how importin α1/β recognizes TDP-43 bipartite nuclear localization signal (NLS). We find that the NLS makes extensive contacts with importin α1, especially at the minor NLS-binding site. NLS binding results in steric clashes with the C terminus of importin α1 that disrupts the TDP-43 N-terminal domain (NTD) dimerization interface. A putative phosphorylation site in the proximity of TDP-43 R83 at the minor NLS site destabilizes binding to importins by reducing …
Mechanisms Of Mitochondrial Promoter Recognition In Humans And Other Mammalian Species, Angelica Zamudio-Ochoa, Yaroslav I Morozov, Azadeh Sarfallah, Michael Anikin, Dmitry Temiakov
Mechanisms Of Mitochondrial Promoter Recognition In Humans And Other Mammalian Species, Angelica Zamudio-Ochoa, Yaroslav I Morozov, Azadeh Sarfallah, Michael Anikin, Dmitry Temiakov
Department of Biochemistry and Molecular Biology Faculty Papers
Recognition of mammalian mitochondrial promoters requires the concerted action of mitochondrial RNA polymerase (mtRNAP) and transcription initiation factors TFAM and TFB2M. In this work, we found that transcript slippage results in heterogeneity of the human mitochondrial transcripts in vivo and in vitro. This allowed us to correctly interpret the RNAseq data, identify the bona fide transcription start sites (TSS), and assign mitochondrial promoters for > 50% of mammalian species and some other vertebrates. The divergent structure of the mammalian promoters reveals previously unappreciated aspects of mtDNA evolution. The correct assignment of TSS also enabled us to establish the precise register of …