Widespread transcript shortening through alternative polyadenylation in secretory cell differentiation

Larry C. Cheng, Dinghai Zheng, Erdene Baljinnyam, Fangzheng Sun, Koichi Ogami, Percy Luk Yeung, Mainul Hoque, Chi-Wei Lu, James L. Manley and Bin Tian ()
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Larry C. Cheng: Rutgers University
Dinghai Zheng: Rutgers New Jersey Medical School
Erdene Baljinnyam: Rutgers New Jersey Medical School
Fangzheng Sun: Rutgers New Jersey Medical School
Koichi Ogami: Columbia University
Percy Luk Yeung: Robert Wood Johnson Medical School and Child Health Institute of New Jersey
Mainul Hoque: Rutgers New Jersey Medical School
Chi-Wei Lu: Robert Wood Johnson Medical School and Child Health Institute of New Jersey
James L. Manley: Columbia University
Bin Tian: Rutgers University

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Most eukaryotic genes produce alternative polyadenylation (APA) isoforms. Here we report that, unlike previously characterized cell lineages, differentiation of syncytiotrophoblast (SCT), a cell type critical for hormone production and secretion during pregnancy, elicits widespread transcript shortening through APA in 3’UTRs and in introns. This global APA change is observed in multiple in vitro trophoblast differentiation models, and in single cells from placentas at different stages of pregnancy. Strikingly, the transcript shortening is unrelated to cell proliferation, a feature previously associated with APA control, but instead accompanies increased secretory functions. We show that 3’UTR shortening leads to transcripts with higher mRNA stability, which augments transcriptional activation, especially for genes involved in secretion. Moreover, this mechanism, named secretion-coupled APA (SCAP), is also executed in B cell differentiation to plasma cells. Together, our data indicate that SCAP tailors the transcriptome during formation of secretory cells, boosting their protein production and secretion capacity.

Date: 2020
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DOI: 10.1038/s41467-020-16959-2

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