Immunoglobulin expression and the humoral immune response is regulated by the non-canonical poly(A) polymerase TENT5C

Aleksandra Bilska, Monika Kusio-Kobiałka, Paweł S. Krawczyk, Olga Gewartowska, Bartosz Tarkowski, Kamil Kobyłecki, Dominika Nowis, Jakub Golab, Jakub Gruchota, Ewa Borsuk, Andrzej Dziembowski () and Seweryn Mroczek ()
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Aleksandra Bilska: University of Warsaw
Monika Kusio-Kobiałka: University of Warsaw
Paweł S. Krawczyk: Polish Academy of Sciences
Olga Gewartowska: Polish Academy of Sciences
Bartosz Tarkowski: Polish Academy of Sciences
Kamil Kobyłecki: Polish Academy of Sciences
Dominika Nowis: Medical University of Warsaw
Jakub Golab: Medical University of Warsaw
Jakub Gruchota: Polish Academy of Sciences
Ewa Borsuk: Polish Academy of Sciences
Andrzej Dziembowski: University of Warsaw
Seweryn Mroczek: University of Warsaw

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15835-3

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DOI: 10.1038/s41467-020-15835-3

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