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  1. Book ; Online ; Thesis: Mechanisms contributing to RNA localization and translation: study of neuronal zipcodes in primary cortical neurons, and translational changes in neurodegeneration

    Mendonsa, Samantha Annamarie [Verfasser]

    2023  

    Author's details Samantha Mendonsa
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Freie Universität Berlin
    Publishing place Berlin
    Document type Book ; Online ; Thesis
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  2. Article ; Online: Charcot-Marie-Tooth mutation in glycyl-tRNA synthetase stalls ribosomes in a pre-accommodation state and activates integrated stress response.

    Mendonsa, Samantha / von Kuegelgen, Nicolai / Bujanic, Lucija / Chekulaeva, Marina

    Nucleic acids research

    2021  Volume 49, Issue 17, Page(s) 10007–10017

    Abstract: Toxic gain-of-function mutations in aminoacyl-tRNA synthetases cause a degeneration of peripheral motor and sensory axons, known as Charcot-Marie-Tooth (CMT) disease. While these mutations do not disrupt overall aminoacylation activity, they interfere ... ...

    Abstract Toxic gain-of-function mutations in aminoacyl-tRNA synthetases cause a degeneration of peripheral motor and sensory axons, known as Charcot-Marie-Tooth (CMT) disease. While these mutations do not disrupt overall aminoacylation activity, they interfere with translation via an unknown mechanism. Here, we dissect the mechanism of function of CMT mutant glycyl-tRNA synthetase (CMT-GARS), using high-resolution ribosome profiling and reporter assays. We find that CMT-GARS mutants deplete the pool of glycyl-tRNAGly available for translation and inhibit the first stage of elongation, the accommodation of glycyl-tRNA into the ribosomal A-site, which causes ribosomes to pause at glycine codons. Moreover, ribosome pausing activates a secondary repression mechanism at the level of translation initiation, by inducing the phosphorylation of the alpha subunit of eIF2 and the integrated stress response. Thus, CMT-GARS mutant triggers translational repression via two interconnected mechanisms, affecting both elongation and initiation of translation.
    MeSH term(s) Cell Line ; Charcot-Marie-Tooth Disease/genetics ; Eukaryotic Initiation Factor-2/metabolism ; Gain of Function Mutation/genetics ; Gene Expression/genetics ; Glycine/genetics ; Glycine-tRNA Ligase/genetics ; HEK293 Cells ; Humans ; Peptide Chain Elongation, Translational/genetics ; Peptide Chain Initiation, Translational/genetics ; Phosphorylation ; Protein Biosynthesis/genetics ; RNA, Transfer, Gly/genetics ; Ribosomes/metabolism
    Chemical Substances Eukaryotic Initiation Factor-2 ; RNA, Transfer, Gly ; Glycine-tRNA Ligase (EC 6.1.1.14) ; Glycine (TE7660XO1C)
    Language English
    Publishing date 2021-08-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkab730
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1067: Show issues Location:
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  3. Article ; Online: mRNA stability and m6A are major determinants of subcellular mRNA localization in neurons

    Loedige, Inga / Baranovskii, Artem / Mendonsa, Samantha / Dantsuji, Sayaka / Popitsch, Niko / Breimann, Laura / Zerna, Nadja / Cherepanov, Vsevolod / Milek, Miha / Ameres, Stefan / Chekulaeva, Marina

    Molecular Cell. 2023 July 13,

    2023  

    Abstract: For cells to perform their biological functions, they need to adopt specific shapes and form functionally distinct subcellular compartments. This is achieved in part via an asymmetric distribution of mRNAs within cells. Currently, the main model of mRNA ... ...

    Abstract For cells to perform their biological functions, they need to adopt specific shapes and form functionally distinct subcellular compartments. This is achieved in part via an asymmetric distribution of mRNAs within cells. Currently, the main model of mRNA localization involves specific sequences called “zipcodes” that direct mRNAs to their proper locations. However, while thousands of mRNAs localize within cells, only a few zipcodes have been identified, suggesting that additional mechanisms contribute to localization. Here, we assess the role of mRNA stability in localization by combining the isolation of the soma and neurites of mouse primary cortical and mESC-derived neurons, SLAM-seq, m⁶A-RIP-seq, the perturbation of mRNA destabilization mechanisms, and the analysis of multiple mRNA localization datasets. We show that depletion of mRNA destabilization elements, such as m⁶A, AU-rich elements, and suboptimal codons, functions as a mechanism that mediates the localization of mRNAs associated with housekeeping functions to neurites in several types of neurons.
    Keywords codons ; data collection ; mice ; models ; neurites ; mRNA localization ; mRNA stability ; m6A ; neuron ; AU-rich elements ; AREs ; 5' terminal oligopyrimidine tracts ; 5'TOPs ; RNA-binding proteins ; RBPs ; codon optimality ; zipcodes
    Language English
    Dates of publication 2023-0713
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2023.06.021
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  4. Article ; Online: Massively parallel identification of mRNA localization elements in primary cortical neurons.

    Mendonsa, Samantha / von Kügelgen, Nicolai / Dantsuji, Sayaka / Ron, Maya / Breimann, Laura / Baranovskii, Artem / Lödige, Inga / Kirchner, Marieluise / Fischer, Meret / Zerna, Nadja / Bujanic, Lucija / Mertins, Philipp / Ulitsky, Igor / Chekulaeva, Marina

    Nature neuroscience

    2023  Volume 26, Issue 3, Page(s) 394–405

    Abstract: Cells adopt highly polarized shapes and form distinct subcellular compartments in many cases due to the localization of many mRNAs to specific areas, where they are translated into proteins with local functions. This mRNA localization is mediated by ... ...

    Abstract Cells adopt highly polarized shapes and form distinct subcellular compartments in many cases due to the localization of many mRNAs to specific areas, where they are translated into proteins with local functions. This mRNA localization is mediated by specific cis-regulatory elements in mRNAs, commonly called 'zipcodes'. Although there are hundreds of localized mRNAs, only a few zipcodes have been characterized. Here we describe a novel neuronal zipcode identification protocol (N-zip) that can identify zipcodes across hundreds of 3' untranslated regions. This approach combines a method of separating the principal subcellular compartments of neurons-cell bodies and neurites-with a massively parallel reporter assay. N-zip identifies the let-7 binding site and (AU)
    MeSH term(s) Mice ; Animals ; RNA, Messenger/metabolism ; Neurons/metabolism ; Neurites
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2023-01-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-022-01243-x
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4891: Show issues Location:
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    Zs.MG 67: Show issues

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  5. Article ; Online: mRNA stability and m

    Loedige, Inga / Baranovskii, Artem / Mendonsa, Samantha / Dantsuji, Sayaka / Popitsch, Niko / Breimann, Laura / Zerna, Nadja / Cherepanov, Vsevolod / Milek, Miha / Ameres, Stefan / Chekulaeva, Marina

    Molecular cell

    2023  Volume 83, Issue 15, Page(s) 2709–2725.e10

    Abstract: For cells to perform their biological functions, they need to adopt specific shapes and form functionally distinct subcellular compartments. This is achieved in part via an asymmetric distribution of mRNAs within cells. Currently, the main model of mRNA ... ...

    Abstract For cells to perform their biological functions, they need to adopt specific shapes and form functionally distinct subcellular compartments. This is achieved in part via an asymmetric distribution of mRNAs within cells. Currently, the main model of mRNA localization involves specific sequences called "zipcodes" that direct mRNAs to their proper locations. However, while thousands of mRNAs localize within cells, only a few zipcodes have been identified, suggesting that additional mechanisms contribute to localization. Here, we assess the role of mRNA stability in localization by combining the isolation of the soma and neurites of mouse primary cortical and mESC-derived neurons, SLAM-seq, m
    MeSH term(s) Animals ; Mice ; RNA, Messenger/genetics ; Neurons ; Neurites ; Codon ; RNA Stability
    Chemical Substances RNA, Messenger ; Codon
    Language English
    Publishing date 2023-07-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2023.06.021
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5055: Show issues Location:
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