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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
Published on: June 24, 2021
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Widespread transcript shortening through alternative polyadenylation in secretory cell differentiation
Larry C Cheng1,2,3, Dinghai Zheng2, Erdene Baljinnyam2
1Graduate Program in Quantitative Biomedicine, School of Graduate Studies, Rutgers University, New Brunswick, NJ 08901, USA.
Nature Communications
|June 25, 2020
Summary
Most eukaryotic genes have alternative polyadenylation (APA) isoforms. This study reveals a new mechanism, secretion-coupled APA (SCAP), that shortens transcripts to boost protein secretion in specialized cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Alternative polyadenylation (APA) is common in eukaryotic gene expression, generating transcript diversity.
- APA typically involves shortening of 3' untranslated regions (3'UTRs).
- Cell proliferation has been linked to APA regulation in some contexts.
Purpose of the Study:
- To investigate APA dynamics during syncytiotrophoblast (SCT) differentiation.
- To identify novel mechanisms regulating APA in secretory cell formation.
- To understand how APA influences gene expression and cellular function in pregnancy and immunity.
Main Methods:
- Analysis of APA isoforms in vitro trophoblast differentiation models.
- Single-cell analysis of placental cells across gestation.
- mRNA stability assays and transcriptional activation studies.
- Investigation of APA in B cell differentiation to plasma cells.
Main Results:
- Syncytiotrophoblast (SCT) differentiation involves widespread transcript shortening via APA in 3'UTRs and introns.
- This transcript shortening is linked to increased secretory functions, not cell proliferation.
- Shortened 3'UTRs enhance mRNA stability and transcriptional activation of secretory genes.
- The secretion-coupled APA (SCAP) mechanism is also observed in B cell differentiation.
Conclusions:
- Secretion-coupled APA (SCAP) is a novel mechanism that optimizes transcriptomes for secretory cell function.
- SCAP enhances protein production and secretion capacity during the formation of specialized cells like SCT and plasma cells.
- This finding reveals a conserved strategy for boosting cellular secretion across different biological systems.
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