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Series GSE151173 Query DataSets for GSE151173
Status Public on May 06, 2023
Title Investigation of diurnal polyadenylation site usage reveals differential regulation in the transcription of gene isoforms
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Other
Summary Gene isoforms are mRNAs produced from the same locus, but that differ in their transcription start sites, protein coding DNA sequences, and/or untranslated regions. Consequently, different isoforms of the same gene can have altered gene function or even serve different biological functions. Conventional RNA-Seq strategies cannot accurately distinguish expression levels between distinct isoforms, and differences in gene expression studies almost always report total gene expression. However, increasing evidence indicates that differences in isoform usage may be important for the regulation of biological functions and for development of diseases such as cancer. Here, we aimed to define whether gene isoforms are subjected to differential regulation and expression by characterizing 24-hour rhythms in polyadenylation site (PAS) usage over the course of the day in the mouse liver. Conventional RNA-Seq experiments have shown that 15-30% of genes in the mouse liver are rhythmically expressed, and it is assumed that the comprising isoforms are expressed in a similar pattern. By performing 3‟-end mRNA-Seq and using stringent criteria for defining differential rhythmic expression, we show that 15% of the genes with more than one PAS exhibit differential rhythmic expression. In particular, many genes known to be rhythmic in the mouse liver harbor at least one constitutively expressed isoform, while several hundred genes characterized as arrhythmically expressed also exhibit a rhythmic isoform. Analysis of PAS usage in nuclear mRNA and single-cell data reveals that the vast majority of isoform-specific regulation does not involve post-transcriptional regulation (e.g., miRNA targeting, RNA half-life) or cell subtype-specific differences in expression. Finally, characterization of PAS usage in Bmal1-/- mice revealed that co-transcriptional regulation plays a large role in the expression of specific gene isoforms. Taken together, our results indicate that gene isoforms can be differentially regulated, and imply that gene isoforms can behave as distinct transcriptional units. Furthermore, our data suggest that conventional RNA-Seq strategies are not the most appropriate choice for detecting changes in gene isoform expression.
 
Overall design 3' mRNA sequencing on WT total, nuclear, and polysomal RNA and Bmal1-/- total RNA from ad libitum-fed mice livers at 6 timepoints in sextuplicate
 
Contributor(s) Greenwell BJ, Menet JS
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Submission date May 26, 2020
Last update date May 06, 2023
Contact name Jerome Menet
E-mail(s) menetlab@gmail.com
Organization name Texas A&M University
Department Biology
Lab Menet Laboratory
Street address Texas A&M University Biology Department 3258 TAMU College Station, TX 77843
City College Station
State/province Texas
ZIP/Postal code 77843
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (144)
GSM4567718 Liver, WT1ZT02
GSM4567719 Liver, WT1ZT06
GSM4567720 Liver, WT1ZT10
Relations
BioProject PRJNA635033
SRA SRP264763

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE151173_Gene_RAW_Table.txt.gz 3.4 Mb (ftp)(http) TXT
GSE151173_Gene_TMM_Table.txt.gz 10.1 Mb (ftp)(http) TXT
GSE151173_PAS_RAW_Table.txt.gz 9.2 Mb (ftp)(http) TXT
GSE151173_PAS_TMM_Table.txt.gz 36.8 Mb (ftp)(http) TXT
GSE151173_PAS_filtered.bed.gz 298.1 Kb (ftp)(http) BED
GSE151173_PAS_unfiltered.bed.gz 831.0 Kb (ftp)(http) BED
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