Proteomics

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The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in multiple myeloma


ABSTRACT: FAM46C is one of the most frequently mutated genes in multiple myeloma (MM). Here, using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active non-canonical poly(A) polymerase which enhances mRNA stability and gene expression. Reintroduction of active FAM46C into MM cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induces cell death. Moreover, silencing of FAM46C in MM cells expressing WT protein enhance cell proliferation. Finally, using a FAM46C-FLAG knock-in mouse strain we show that the FAM46C protein is strongly induced during activation of primary splenocytes and that B lymphocytes isolated from newly generated FAM46C KO mice proliferate faster than those isolated from their WT littermates. Concluding, our data clearly indicate that FAM46C works as an onco-suppressor, with the specificity for B-lymphocyte lineage from which multiple myeloma originates.

OTHER RELATED OMICS DATASETS IN: PRJNA326952

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Epithelial Cell, Cell Culture

DISEASE(S): Multiple Myeloma

SUBMITTER: Dominik Cysewski  

LAB HEAD: Andrzej Dziembowski

PROVIDER: PXD006790 | Pride | 2018-03-09

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
305211207mro_0.raw Raw
305291226mro_skmm1_fam46wt.raw Raw
305291230mro_fam_Cwt.raw Raw
305291233mro_fam_Cmut.raw Raw
306081439mro_puste1.raw Raw
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Publications

The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in multiple myeloma.

Mroczek Seweryn S   Chlebowska Justyna J   Kuliński Tomasz M TM   Gewartowska Olga O   Gruchota Jakub J   Cysewski Dominik D   Liudkovska Vladyslava V   Borsuk Ewa E   Nowis Dominika D   Dziembowski Andrzej A  

Nature communications 20170920 1


FAM46C is one of the most frequently mutated genes in multiple myeloma. Here, using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active non-canonical poly(A) polymerase which enhances mRNA stability and gene expression. Reintroduction of active FAM46C into multiple myeloma cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted p  ...[more]

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