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

Quantitative Biology - 2018
Ayşegül Güvenek1, Bin Tian1
1<sup>1</sup>. Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA

Tóm tắt

BackgroundMost 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).MethodsUsing 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.ResultsWe 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.ConclusionTogether, 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.

Từ khóa


Tài liệu tham khảo

10.1038/nrm.2016.116

10.1002/wrna.116

10.1101/gad.261974.115

10.1038/nmeth.2288

10.1101/gr.132563.111

10.1038/nature07509

10.1186/gb‐2005‐6‐12‐r100

10.1101/gr.146886.112

10.1186/s12915‐016‐0229‐6

10.1073/pnas.0900028106

10.1016/j.cell.2009.06.016

10.1126/science.1155390

10.1038/s41598‐017‐17407‐w

10.1016/j.neuron.2008.11.029

10.1002/wrna.47

10.1016/j.tcb.2015.10.012

10.7554/eLife.10782

10.1101/gad.207456.112

10.1016/j.cell.2008.05.045

10.1073/pnas.1002929107

10.1016/j.molcel.2016.01.020

10.1016/j.tcb.2009.06.001

10.1016/j.neuron.2018.03.030

10.1016/j.cell.2012.03.022

10.1101/gad.229328.113

10.1261/rna.2581711

10.1261/rna.057075.116

10.1186/s12859‐016‐1254‐8

10.1038/nmeth.1528

10.1186/s12864‐017‐4241‐1

10.1016/j.ymeth.2015.04.011

10.1093/bioinformatics/btu189

10.1038/ncomms6274

10.1093/nar/gkx1000

10.1101/gr.133744.111

10.1523/JNEUROSCI.1860‐14.2014

10.1016/j.molcel.2009.09.043

10.1038/nrm2690

10.1126/science.aaa1934

10.1371/journal.pgen.1002090

10.1038/ng.1036

10.15252/msb.20145508

10.1016/j.celrep.2017.10.095

10.1186/s13395‐017‐0122‐1

10.1093/nar/gkx800

10.1074/jbc.M112.366195

10.1038/sj.bjc.6604356

10.1038/ncomms6212

10.1101/gad.1799609

10.1371/journal.pone.0008419

10.1371/journal.pgen.1005166

10.1101/gr.5532707

10.1016/j.molcel.2011.01.022

10.1038/msb.2011.69

10.1073/pnas.1112672108

10.1016/j.molcel.2014.11.024

10.1038/ncomms8576

10.1038/nmeth.1923

10.1093/bioinformatics/bts635

10.1186/gb‐2010‐11‐10‐r106

Thông tin
Thông tin xuất bản

Quantitative Biology

Thông tin tác giả