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| Status |
Public on Aug 08, 2018 |
| Title |
A compendium of conserved cleavage and polyadenylation events in mammalian genes |
| Organisms |
Homo sapiens; Mus musculus; Rattus norvegicus |
| Experiment type |
Other
|
| Summary |
Cleavage and polyadenylation is essential for 3’ end processing of almost all eukaryotic mRNAs. Recent studies have shown widespread alternative cleavage and polyadenylation (APA) events leading to mRNA isoforms with different 3’UTRs and/or coding sequences. Here we present a compendium of conserved cleavage and polyadenylation sites (PASs) in mammalian genes, based on ~1.2 billion 3’ end sequencing reads from over 360 human, mouse and rat samples. We show that ~80% of mammalian mRNA genes contain at least one conserved PAS, and ~50% have conserved APA events. PAS conservation generally reduces promiscuous 3’ end processing, stabling gene expression levels across species. Conservation of APA correlates with gene age, gene expression features, and gene functions. Genes with certain functions, such as cell morphology, cell proliferation, and mRNA metabolism, are particularly enriched with APA events. While tissue-specific genes typically have a low APA rate, brain-specific genes tend to evolve APA. We show enrichment of mRNA destabilizing motifs in alternative 3’UTR sequences, leading to substantial differences in mRNA stability between 3’UTR APA isoforms. Using conserved PASs, we reveal sequence motifs surrounding APA sites and a preference of adenosine at the cleavage site. Mutations of the U-rich motif around the PAS often accompany APA profile changes between species. Analysis of lncRNA PASs indicates a mechanism of PAS fixation involving evolution of A-rich motifs. Taken together, our results present a comprehensive view of PAS evolution in mammals, and a phylogenic understanding of APA functions.
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| Overall design |
21 3'READS libraries for the analysis of APA in heart, testis and heart between mouse and rat
107 3'READS human samples used in PolyA_DB version 3.2
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| Contributor(s) |
Wang R, Zheng D, Yehia G, Tian B |
| Citation(s) |
30143597 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 GM084089 |
Regulation of Alternatiive Cleavage and Polyadenylation |
RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY--RBHS-NEW JERSEY MEDICAL SCHOOL |
BIN TIAN |
|
| Submission date |
Feb 26, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Bin Tian |
| E-mail(s) |
btian@rutgers.edu
|
| Organization name |
Rutgers New Jersey Medical School
|
| Department |
Department of Microbiology, Biochemistry and Molecular Genetics
|
| Street address |
205 South Orange Ave.
|
| City |
Newark |
| State/province |
NJ |
| ZIP/Postal code |
07103 |
| Country |
USA |
| |
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| Platforms (5)
|
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
|
| Samples (128)
|
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| Relations |
| BioProject |
PRJNA435992 |
| SRA |
SRP133500 |
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