B cell humoral response and differentiation is regulated by the non-canonical poly(A) polymerase TENT5C
| Autor: | Bartosz Tarkowski, Pawel S. Krawczyk, Ewa Borsuk, Aleksandra Bilska, Andrzej Dziembowski, Monika Kusio-Kobiałka, Kamil Kobyłecki, Jakub Gruchota, Seweryn Mroczek, Olga Gewartowska |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Messenger RNA biology Chemistry 3. Good health Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Downregulation and upregulation 030220 oncology & carcinogenesis Humoral immunity Unfolded protein response biology.protein medicine Secretion Antibody B cell Secretory pathway 030304 developmental biology |
| DOI: | 10.1101/686683 |
| Popis: | SummaryTENT5C is a non-canonical cytoplasmic poly(A) polymerase (ncPAP) upregulated in activated B cells and suppressing their proliferation. Herein we measured the global distribution of poly(A) tail lengths in responsive B cells using a modified Nanopore direct RNA-sequencing approach and revealed that TENT5C polyadenylates immunoglobulin mRNAs regulating their steady-state levels. Consequently, TENT5C deficient B cells secrete less antibodies and KO mice have diminished gamma globulin concentrations despite the increased number of CD138high plasma cells as a consequence of accelerated differentiation. TENT5C is explicitly upregulated in differentiating plasma cells by innate signaling. Importantly, TENT5C deficiency in B lymphocytes impairs the capacity of the secretory pathway through the reduction of ER volume and downregulation of unfolded protein response.Our findings define the role of the TENT5C enzyme in B cell physiology and discover the first ncPAP engaged in the regulation of immunoglobulin mRNA poly(A) tails, thus serving as a regulator of humoral immunity. |
| Databáze: | OpenAIRE |
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