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Quantitative Biology

, Volume 6, Issue 3, pp 253–266 | Cite as

Analysis of alternative cleavage and polyadenylation in mature and differentiating neurons using RNA-seq data

  • Aysegul Guvenek
  • Bin Tian
Research Article
  • 113 Downloads

Abstract

Background

Most eukaryotic protein-coding genes exhibit alternative cleavage and polyadenylation (APA), resulting in mRNA isoforms with different 3′ untranslated regions (3′ UTRs). Studies have shown that brain cells tend to express long 3′ UTR isoforms using distal cleavage and polyadenylation sites (PASs).

Methods

Using our recently developed, comprehensive PAS database PolyA_DB, we developed an efficient method to examine APA, named Significance Analysis of Alternative Polyadenylation using RNA-seq (SAAP-RS). We applied this method to study APA in brain cells and neurogenesis.

Results

We found that neurons globally express longer 3′ UTRs than other cell types in brain, and microglia and endothelial cells express substantially shorter 3′ UTRs. We show that the 3′ UTR diversity across brain cells can be corroborated with single cell sequencing data. Further analysis of APA regulation of 3′ UTRs during differentiation of embryonic stem cells into neurons indicates that a large fraction of the APA events regulated in neurogenesis are similarly modulated in myogenesis, but to a much greater extent.

Conclusion

Together, our data delineate APA profiles in different brain cells and indicate that APA regulation in neurogenesis is largely an augmented process taking place in other types of cell differentiation.

Keywords

alternative polyadenylation brain cells RNA-seq scRNA-seq 

Notes

Acknowledgments

We thank members of Bin Tian lab for helpful discussions. This work was supported by grants from NIH (Nos. R01 GM084089 and R21 NS097992) and a grant from the Rutgers Brain Health Institute.

Supplementary material

40484_2018_148_MOESM1_ESM.pdf (1.5 mb)
Analysis of alternative cleavage and polyadenylation in mature and differentiating neurons using RNA-seq data

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Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Microbiology, Biochemistry and Molecular GeneticsRutgers New Jersey Medical SchoolNewarkUSA
  2. 2.Rutgers School of Graduate StudiesNewarkUSA
  3. 3.Rutgers Cancer Institute of New JerseyNewarkUSA
  4. 4.Rutgers Brain Health InstituteNewarkUSA

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