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Status |
Public on Sep 28, 2023 |
Title |
Olfactory receptor mRNAs act as selfish non-coding RNAs that enforce transcriptional singularity (Non-coding OR Hi-C & RNA-seq) |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
To investigate roles for olfactory receptor coding sequence mRNA in trans olfactory receptor gene silencing, and OR-gene enhancer recruitment. Olfactory receptor (OR) choice provides an extreme example of allelic competition for transcriptional dominance, as every olfactory neuron stably transcribes one out of more than ~2,000 OR alleles1,2. OR gene choice is mediated by a multi-chromosomal enhancer hub that activates transcription at a single OR3,4, followed by ORtranslation dependent feedback that stabilizes this choice5,6. However, with more than one OR enhancer hub in each nucleus7, the mechanism by which only one OR allele is chosen for transcription remains enigmatic. Here, using single cell genomics, we show that only one of the OR enhancer hubs formed in each neuron retains euchromatic features and sustains transcriptional competence. Further, we provide evidence that OR transcription recruits enhancers and reinforces enhancer hub activity locally, while OR RNA inhibits transcription in competing hubs over distance, promoting OR protein-independent transition to singularity. While OR RNA synthesis is sufficient to break the symmetry between equipotent enhancer hubs, OR translation stabilizes transcription at the prevailing hub, revealing dual non-coding and coding mechanisms implemented by OR RNAs for transcriptional prevalence. We propose that coding mRNAs can function as “selfish” non-coding RNAs that influence nuclear architecture, enhance their own transcription, and inhibit their competitors, with generalizable implications in probabilistic cell fate decisions.
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Overall design |
CRISPR and transgene creation were used to generate inducible noncoding olfactory receptor genes to test the role of olfactory receptor RNA in olfactory receptor gene silencing and enhancer hub formation, which were assessed by performing RNA-seq and Hi-C.
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Web link |
https://pubmed.ncbi.nlm.nih.gov/38123679/
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Contributor(s) |
Pourmorady A, Lomvardas S |
Citation(s) |
38123679 |
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Submission date |
May 10, 2023 |
Last update date |
Dec 28, 2023 |
Contact name |
Ariel Pourmorady |
E-mail(s) |
adp2164@columbia.edu, arielpourmorady@gmail.com
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Organization name |
Columbia University
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Department |
Neurobiology and Behavior
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Lab |
Lomvardas Lab
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Street address |
3227 Broadway
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10027 |
Country |
USA |
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Platforms (3) |
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Samples (41)
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GSM7317667 |
gg8tTAtetOP2(nc), control HiC, r2 |
GSM7317668 |
OMPtTAtetOP2, control HiC, r1 |
GSM7317669 |
OMPtTAtetOP2, control HiC, r2 |
GSM7317670 |
OMPiGFP/Atf5iRFP, control HiC, r1 |
GSM7317671 |
OMPiGFP/Atf5iRFP, control HiC, r2 |
GSM7317672 |
OMPiGFP/Atf5iRFP, RNA-seq, r1 |
GSM7317673 |
OMPiGFP/Atf5iRFP, RNA-seq, r2 |
GSM7317674 |
Krt5CreERrosa26tdT, RNA-seq, r1 |
GSM7317675 |
Krt5CreERrosa26tdT, RNA-seq, r2 |
GSM7317676 |
Mash1iCrerosa26tdT, RNA-seq, r1 |
GSM7317677 |
Mash1iCrerosa26tdT, RNA-seq, r2 |
GSM7317678 |
Mash1iCrerosa26tdT/Ngn1GFP, RNA-seq, r1 |
GSM7317679 |
Mash1iCrerosa26tdT/Ngn1GFP, RNA-seq, r2 |
GSM7317680 |
Ngn1iGFP, RNA-seq, r1 |
GSM7317681 |
Ngn1iGFP, RNA-seq, r2 |
GSM7317682 |
OMPiGFP, RNA-seq, r1 |
GSM7317683 |
OMPiGFP, RNA-seq, r2 |
GSM7317684 |
OMPtTAtetOP2, RNA-seq, r1 |
GSM7317685 |
OMPtTAtetOP2(nc), RNA-seq, r1 |
GSM7317686 |
gg8tTAtetOP2(nc), RNA-seq, r2 |
GSM7317687 |
gg8tTAtetOP2, RNA-seq, r1 |
GSM7317688 |
gg8tTAtetOP2(nc), RNA-seq, r3 |
GSM7317689 |
OMPtTAtetOP2, RNA-seq, r2 |
GSM7317690 |
OMPtTAtetOP2(nc), RNA-seq, r2 |
GSM7317691 |
OMPtTAtetOP2(nc), RNA-seq, r3 |
GSM7317692 |
gg8tTAtetOP2(nc), RNA-seq, r4 |
GSM7317693 |
OMPtTAtetOGFP, RNA-seq, r1 |
GSM7317694 |
OMPtTAtetOGFP, RNA-seq, r2 |
GSM7317695 |
gg8tTAtetOGFP, RNA-seq, r1 |
GSM7317696 |
gg8tTAtetOGFP, RNA-seq, r2 |
GSM7701353 |
OMPtTAtetOP2(nc), control HiC, r1 |
GSM7701354 |
OMPtTAtetOP2(nc), control HiC, r2 |
GSM7844456 |
OMPiGFP, RNA-seq, r1 |
GSM7844457 |
OMPiGFP, RNA-seq, r2 |
GSM7844458 |
OMPiGFP, RNA-seq, r3 |
GSM7844459 |
OMPiGFP/OMPtTA, RNA-seq, r1 |
GSM7844460 |
OMPiGFP/OMPtTA, RNA-seq, r2 |
GSM7844461 |
OMPiGFP/OMPtTA, RNA-seq, r3 |
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This SubSeries is part of SuperSeries: |
GSE230380 |
Olfactory receptor mRNAs act as selfish non-coding RNAs that enforce transcriptional singularity |
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Relations |
BioProject |
PRJNA971200 |
Supplementary file |
Size |
Download |
File type/resource |
GSE232194_HiC.Atf5-TR-WT.iRFP.mm10.mapq_30.1000.mcool |
1.2 Gb |
(ftp)(http) |
MCOOL |
GSE232194_OMPtTA.tetOP2.NormalFood.ImmediateFix.Liquid.HiC.AP60.AP94.merge.mm10.mapq_30.1000.mcool |
1.5 Gb |
(ftp)(http) |
MCOOL |
GSE232194_OMPtTAtetOM71KO.AP145.AP146.mm10.mapq_30.1000.mcool |
806.4 Mb |
(ftp)(http) |
MCOOL |
GSE232194_OMPtTAtetOP2KO.AP187.AP188_230921.mm10.mapq_30.1000.mcool |
1.3 Gb |
(ftp)(http) |
MCOOL |
GSE232194_gg8tTAtetOP2KO.GFPPos.AP147.AP149.mm10.mapq_30.1000.mcool |
770.5 Mb |
(ftp)(http) |
MCOOL |
GSE232194_rlog_rna_dev.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
GSE232194_rlog_rna_mutants.txt.gz |
3.2 Mb |
(ftp)(http) |
TXT |
GSE232194_rna.OMPM71nc_v_OMPGFPOMPtTA_rlog_rna.txt.gz |
377.7 Kb |
(ftp)(http) |
TXT |
GSE232194_rna.OMPM71nc_v_OMPGFP_rlog_rna.txt.gz |
389.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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