B-cell humoral response and differentiation is regulated by non-canonical poly(A) polymerase TENT5C

Bilska, A.; Kusio-Kobialka, M.; Krawczyk, P. S.; Gewartowska, O.; Tarkowski, B.; Kobylecki, K.; Gruchota, J.; Borsuk, E.; Dziembowski, A.; Mroczek, S.

doi:10.1101/686683

bioRxiv · 10.1101/686683

B-cell humoral response and differentiation is regulated by non-canonical poly(A) polymerase TENT5C

Bilska, A.·Kusio-Kobialka, M.·Krawczyk, P. S.·Gewartowska, O.·Tarkowski, B.·Kobylecki, K.·Gruchota, J.·Borsuk, E.·Dziembowski, A.·Mroczek, S.

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Abstract

TENT5C 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.\n\nOur 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.

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Bilska, A., Kusio-Kobialka, M., Krawczyk, P. S., Gewartowska, O., Tarkowski, B., Kobylecki, K., Gruchota, J., Borsuk, E., Dziembowski, A., Mroczek, S.. 2019-07-09. B-cell humoral response and differentiation is regulated by non-canonical poly(A) polymerase TENT5C. https://doi.org/10.1101/686683

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