Immunoglobulin expression and the humoral immune response is regulated by the non-canonical poly(A) polymerase TENT5C
| Autor: | Bartosz Tarkowski, Seweryn Mroczek, Andrzej Dziembowski, Jakub Golab, Monika Kusio-Kobiałka, Ewa Borsuk, Dominika Nowis, Kamil Kobyłecki, Jakub Gruchota, Pawel S. Krawczyk, Olga Gewartowska, Aleksandra Bilska |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Polyadenylation Science Cellular differentiation General Physics and Astronomy Immunoglobulins 02 engineering and technology General Biochemistry Genetics and Molecular Biology Gene Expression Regulation Enzymologic Article Antibodies 03 medical and health sciences Mice Immune system Animals RNA-Seq lcsh:Science Polymerase Mice Knockout Messenger RNA B-Lymphocytes Multidisciplinary biology Chemistry Cell Differentiation RNA sequencing General Chemistry 021001 nanoscience & nanotechnology RNA modification Nucleotidyltransferases Cell biology Immunity Humoral 030104 developmental biology Phenotype biology.protein Unfolded protein response Unfolded Protein Response lcsh:Q Female Antibody Signal transduction 0210 nano-technology Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) |
| ISSN: | 2041-1723 |
| Popis: | TENT5C is a non-canonical cytoplasmic poly(A) polymerase highly expressed by activated B cells to suppress their proliferation. Here we measure the global distribution of poly(A) tail lengths in responsive B cells using a Nanopore direct RNA-sequencing approach, showing that TENT5C polyadenylates immunoglobulin mRNAs regulating their half-life and consequently steady-state levels. TENT5C is upregulated in differentiating plasma cells by innate signaling. Compared with wild-type, Tent5c−/− mice produce fewer antibodies and have diminished T-cell-independent immune response despite having more CD138high plasma cells as a consequence of accelerated differentiation. B cells from Tent5c−/− mice also have impaired capacity of the secretory pathway, with reduced ER volume and unfolded protein response. Importantly, these functions of TENT5C are dependent on its enzymatic activity as catalytic mutation knock-in mice display the same defect as Tent5c−/−. These findings define the role of the TENT5C enzyme in the humoral immune response. Regulating polyadenylation is important for mRNA stability, which can in turn affect B cell maturation and humoral immune responses. Here the authors use Nanopore poly(A) sequencing to explore the importance of the cytoplasmic poly(A) polymerase TENT5C, particularly in the production of immunoglobulins. |
| Databáze: | OpenAIRE |
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