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GSE295421

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Enhancing RNA base editing on mammalian transcripts with small nuclear RNAs

Organism: Homo sapiens
Platform: GPL34284
Samples: 10
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Apr 23 2025
Last Updated: Oct 02 2025
Status: Public on Jul 03 2025
Contact: Brian,,Yee (UCSD)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1254645

Summary

Endogenous Uridine-rich small nuclear RNAs (U snRNAs) form RNA-protein complexes to process eukaryotic pre-mRNA into mRNA. Previous studies have demonstrated programmable U snRNA guide-targeted exon inclusion and exclusion. We investigated whether snRNAs can also enhance RNA base editing over state-of-the-art RNA-targeting technologies in human cells. Compared to adenosine deaminase acting on RNA (ADAR)-recruiting circular RNAs, we find that guided A>I snRNAs consistently increase adenosine-to-inosine editing for higher exon count genes, perturb substantially fewer off-target genes, and localize more persistently to the nucleus where ADAR is expressed. A>I snRNAs also more efficiently edit lncRNAs and pre-mRNA 3′ splice sites to promote splicing changes. Finally, snRNA-H/ACA box snoRNA fusions (U>Ψ snRNAs) increase targeted RNA pseudouridylation without DKC1 overexpression, facilitating improved CFTR rescue from nonsense-mediated mRNA decay in a Cystic fibrosis human bronchial epithelial cell model. Our results advance the endogenous protein-mediated RNA base editing toolbox and RNA-targeting technologies to treat genetic diseases.

Overall Design

RNA-seq of human HEK 293T cells following transfection with plasmids encoding pUC19 (empty vector), U7 promoter-driven U7smOPT snRNA (targeting DMD and RAB7A) in pUC19, and U6 promoter-driven cadRNA (targeting DMD and RAB7A) in pUC19

Analysis (3 steps)

View Data Processing
Processing steps for GSE295421
  1. Reads were mapped using STAR 2.7.6a
  2. Read count extraction was performed using featureCounts from the Subread package, with results sorted into counts matrices
  3. Differential gene expression analysis was performed on the counts matrices using DESeq2

Supplementary Files (4)

GSE295421_dmd_cad.txt.gz Download
GSE295421_dmd_u7.txt.gz Download
GSE295421_rab7a_cad.txt.gz Download
GSE295421_rab7a_u7.txt.gz Download
GEO Samples (10)
GSM8947637 GSM8947638 GSM8947639 GSM8947640 GSM8947641 GSM8947642 GSM8947643 GSM8947644 GSM8947645 GSM8947646

Dataset Citations (1)

Enhancing RNA base editing on mammalian transcripts with small nuclear RNAs.
PMID 40968292 · 2025 · Nature chemical biology
Aaron A Smargon, Deepak Pant, Trent A Gomberg, Christian Fagre, Sofia Glynne, Johnathan Nguyen, Jack T Naritomi, Wendy V Gilbert, Gene W Yeo

SRA Experiments (10) and Runs (10)

Total: 24546 MB
SRX28530139 SRP580767 RNA-Seq PAIRED
GSM8947637: pUC19 biol rep 1; Homo sapiens; RNA-Seq
Sample: SRS24833369
BioProject: PRJNA1254645
BioSample: SAMN48116881
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284753 39995303 8079051206 2305.04 pUC19_rep1_S32_L001_R1_001.fastq.gz, pUC19_rep1_S32_L001_R2_001.fastq… SRA
SRX28530140 SRP580767 RNA-Seq PAIRED
GSM8947638: pUC19 biol rep 2; Homo sapiens; RNA-Seq
Sample: SRS24833370
BioProject: PRJNA1254645
BioSample: SAMN48116880
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284752 44323771 8953401742 2559.4 pUC19_rep2_S33_L001_R1_001.fastq.gz, pUC19_rep2_S33_L001_R2_001.fastq… SRA
SRX28530141 SRP580767 RNA-Seq PAIRED
GSM8947639: DMD cadRNA biol rep 1; Homo sapiens; RNA-Seq
Sample: SRS24833371
BioProject: PRJNA1254645
BioSample: SAMN48116879
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284751 39832451 8046155102 2298.32 DMD_cad_rep1_S10_L001_R1_001.fastq.gz, DMD_cad_rep1_S10_L001_R2_001.f… SRA
SRX28530142 SRP580767 RNA-Seq PAIRED
GSM8947640: DMD cadRNA biol rep 2; Homo sapiens; RNA-Seq
Sample: SRS24833372
BioProject: PRJNA1254645
BioSample: SAMN48116878
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284750 41027573 8287569746 2368.9 DMD_cad_rep3_S11_L001_R1_001.fastq.gz, DMD_cad_rep3_S11_L001_R2_001.f… SRA
SRX28530143 SRP580767 RNA-Seq PAIRED
GSM8947641: DMD U7smOPT snRNA biol rep 1; Homo sapiens; RNA-Seq
Sample: SRS24833373
BioProject: PRJNA1254645
BioSample: SAMN48116877
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284749 43632035 8813671070 2511.04 DMD_U7_rep2_S12_L001_R1_001.fastq.gz, DMD_U7_rep2_S12_L001_R2_001.fas… SRA
SRX28530144 SRP580767 RNA-Seq PAIRED
GSM8947642: DMD U7smOPT snRNA biol rep 2; Homo sapiens; RNA-Seq
Sample: SRS24833374
BioProject: PRJNA1254645
BioSample: SAMN48116876
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284748 43521693 8791381986 2516.44 DMD_U7_rep3_S13_L001_R1_001.fastq.gz, DMD_U7_rep3_S13_L001_R2_001.fas… SRA
SRX28530145 SRP580767 RNA-Seq PAIRED
GSM8947643: RAB7A cadRNA biol rep 1; Homo sapiens; RNA-Seq
Sample: SRS24833375
BioProject: PRJNA1254645
BioSample: SAMN48116875
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284747 42219600 8528359200 2508.09 RAB7A_cad_rep1_S34_L001_R1_001.fastq.gz, RAB7A_cad_rep1_S34_L001_R2_0… SRA
SRX28530146 SRP580767 RNA-Seq PAIRED
GSM8947644: RAB7A cadRNA biol rep 2; Homo sapiens; RNA-Seq
Sample: SRS24833376
BioProject: PRJNA1254645
BioSample: SAMN48116874
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284746 42652632 8615831664 2512.25 RAB7A_cad_rep2_S35_L001_R1_001.fastq.gz, RAB7A_cad_rep2_S35_L001_R2_0… SRA
SRX28530147 SRP580767 RNA-Seq PAIRED
GSM8947645: RAB7A U7smOPT snRNA biol rep 1; Homo sapiens; RNA-Seq
Sample: SRS24833377
BioProject: PRJNA1254645
BioSample: SAMN48116873
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284745 39685660 8016503320 2307.8 RAB7A_U7_rep2_S36_L001_R1_001.fastq.gz, RAB7A_U7_rep2_S36_L001_R2_001… SRA
SRX28530148 SRP580767 RNA-Seq PAIRED
GSM8947646: RAB7A U7smOPT snRNA biol rep 2; Homo sapiens; RNA-Seq
Sample: SRS24833378
BioProject: PRJNA1254645
BioSample: SAMN48116872
Platform: ILLUMINA
Instrument: Illumina NovaSeq X Plus
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
cell line: HEK293T
geo_loc_name: missing
collection_date: missing
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR33284744 45843315 9260349630 2658.97 RAB7A_U7_rep3_S37_L001_R1_001.fastq.gz, RAB7A_U7_rep3_S37_L001_R2_001… SRA

Linked Publications (2)

Enhancing RNA base editing on mammalian transcripts with small nuclear RNAs.
Nature chemical biology · 2025
Enhancing RNA base editing on mammalian transcripts with small nuclear RNAs.
Nature chemical biology · 2025

Data Files (10)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— DMD_cad_rep1_S10_L001_R1_001.fastq.gz RNA-Seq 2.2 GB link
— DMD_cad_rep3_S11_L001_R1_001.fastq.gz RNA-Seq 2.3 GB link
— DMD_U7_rep2_S12_L001_R1_001.fastq.gz RNA-Seq 2.5 GB link
— DMD_U7_rep3_S13_L001_R1_001.fastq.gz RNA-Seq 2.5 GB link
— pUC19_rep1_S32_L001_R1_001.fastq.gz RNA-Seq 2.3 GB link
— pUC19_rep2_S33_L001_R1_001.fastq.gz RNA-Seq 2.5 GB link
— RAB7A_cad_rep1_S34_L001_R1_001.fastq.gz RNA-Seq 2.4 GB link
— RAB7A_cad_rep2_S35_L001_R1_001.fastq.gz RNA-Seq 2.5 GB link
— RAB7A_U7_rep2_S36_L001_R1_001.fastq.gz RNA-Seq 2.3 GB link
— RAB7A_U7_rep3_S37_L001_R1_001.fastq.gz RNA-Seq 2.6 GB link