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Disruption in A-to-I Editing Levels Affects C. elegans Development More Than a Complete Lack of Editing.

Cell reports · 2019 · Vol. 27 (4) · pp. 1244-1253.e4

Abstract

A-to-I RNA editing, catalyzed by ADAR proteins, is widespread in eukaryotic transcriptomes. Studies showed that, in C. elegans, ADR-2 can actively deaminate dsRNA, whereas ADR-1 cannot. Therefore, we set out to study the effect of each of the ADAR genes on the RNA editing process. We performed comprehensive phenotypic, transcriptomics, proteomics, and RNA binding screens on worms mutated in a single ADAR gene. We found that ADR-1 mutants exhibit more-severe phenotypes than ADR-2, and some of them are a result of non-editing functions of ADR-1. We also show that ADR-1 significantly binds edited genes and regulates mRNA expression, whereas the effect on protein levels is minor. In addition, ADR-1 primarily promotes editing by ADR-2 at the L4 stage of development. Our results suggest that ADR-1 has a significant role in the RNA editing process and in altering editing levels that affect RNA expression; loss of ADR-1 results in severe phenotypes.

Publication Types

["Journal Article", "Research Support, N.I.H., Extramural", "Research Support, Non-U.S. Gov't"]

Keywords

MeSH Terms

["Adenosine", "Adenosine Deaminase", "Animals", "Caenorhabditis elegans", "Caenorhabditis elegans Proteins", "Inosine", "Mutation", "Phenotype", "Proteome", "RNA Editing", "Transcriptome"]

Funding

P40 OD010440 NIH HHS (United States)
F32 GM119257 NIGMS NIH HHS (United States)
R01 GM130759 NIGMS NIH HHS (United States)

Linked Datasets (1)

GSE110701 GSE via ncbi_elink
GEO

Disruption in A-to-I editing levels affects C. elegans development more than a complete lack of editing

6239
84 data files
FileTypeSize
BB19_embryo_1_131216_CGATGT.fastq.gz RNA-Seq 1.4 GB
BB19_embryo_1_131216_CGATGT.fastq.gz RNA-Seq 1.4 GB
BB19_embryo_2_051216_TTAGGC.fastq.gz RNA-Seq 1.3 GB
BB19_embryo_2_051216_TTAGGC.fastq.gz RNA-Seq 1.3 GB
BB19_embryo_310816_TTAGGC.fastq.gz RNA-Seq 1016.1 MB
BB19_embryo_310816_TTAGGC.fastq.gz RNA-Seq 1016.1 MB
BB19_L4_220816_GCCAAT.fastq.gz RNA-Seq 1.3 GB
BB19_L4_220816_GCCAAT.fastq.gz RNA-Seq 1.3 GB
BB19_L4_6_10_16_TAGCTT.fastq.gz RNA-Seq 1.3 GB
BB19_L4_6_10_16_TAGCTT.fastq.gz RNA-Seq 1.3 GB
BB19_L4_Ayya_GGCTAC.fastq.gz RNA-Seq 1.2 GB
BB19_L4_Ayya_GGCTAC.fastq.gz RNA-Seq 1.2 GB
BB2_E_18_12_16_CAGATC.fastq.gz RNA-Seq 1.3 GB
BB2_E_18_12_16_CAGATC.fastq.gz RNA-Seq 1.3 GB
BB2_embryo_070916_TTAGGC.fastq.gz RNA-Seq 1.2 GB
BB2_embryo_070916_TTAGGC.fastq.gz RNA-Seq 1.2 GB
BB2_L4_221216_ACAGTG.fastq.gz RNA-Seq 1.3 GB
BB2_L4_221216_ACAGTG.fastq.gz RNA-Seq 1.3 GB
BB2_L4_230816_CAGATC.fastq.gz RNA-Seq 1.1 GB
BB2_L4_230816_CAGATC.fastq.gz RNA-Seq 1.1 GB
BB2_L4_Ayya_ATCACG.fastq.gz RNA-Seq 1.1 GB
BB2_L4_Ayya_ATCACG.fastq.gz RNA-Seq 1.1 GB
BB3_E_19_12_16_GATCAG.fastq.gz RNA-Seq 1.2 GB
BB3_E_19_12_16_GATCAG.fastq.gz RNA-Seq 1.2 GB
BB3_embryo_011216_TAGCTT.fastq.gz RNA-Seq 1.3 GB
BB3_embryo_011216_TAGCTT.fastq.gz RNA-Seq 1.3 GB
BB3_embryo_230816_ACAGTG.fastq.gz RNA-Seq 1.3 GB
BB3_embryo_230816_ACAGTG.fastq.gz RNA-Seq 1.3 GB
BB3_L4_10_10_16_ACTTGA.fastq.gz RNA-Seq 1.1 GB
BB3_L4_10_10_16_ACTTGA.fastq.gz RNA-Seq 1.1 GB
BB3_L4_160816_GATCAG.fastq.gz RNA-Seq 1.3 GB
BB3_L4_160816_GATCAG.fastq.gz RNA-Seq 1.3 GB
BB3_L4_Ayya_CTTGTA.fastq.gz RNA-Seq 1.3 GB
BB3_L4_Ayya_CTTGTA.fastq.gz RNA-Seq 1.3 GB
GSF-896-134-Input-24June_S6_R1_001.fastq.gz RIP-Seq 1009.6 MB
GSF-896-134-Input-24June_S6_R1_001.fastq.gz RIP-Seq 1009.6 MB
GSF-896-134-Input-30Mar_S3_R1_001.fastq.gz RIP-Seq 1.8 GB
GSF-896-134-Input-30Mar_S3_R1_001.fastq.gz RIP-Seq 1.8 GB
GSF-896-134-RIP-24June_S15_R1_001.fastq.gz RIP-Seq 760.1 MB
GSF-896-134-RIP-24June_S15_R1_001.fastq.gz RIP-Seq 760.1 MB
GSF-896-134-RIP-30Mar_S12_R1_001.fastq.gz RIP-Seq 792.5 MB
GSF-896-134-RIP-30Mar_S12_R1_001.fastq.gz RIP-Seq 792.5 MB
GSF-896-76-Input-24June_S4_R1_001.fastq.gz RIP-Seq 955.5 MB
GSF-896-76-Input-24June_S4_R1_001.fastq.gz RIP-Seq 955.5 MB
GSF-896-76-Input-30Mar_S1_R1_001.fastq.gz RIP-Seq 1.7 GB
GSF-896-76-Input-30Mar_S1_R1_001.fastq.gz RIP-Seq 1.7 GB
GSF-896-76-RIP-24June_S13_R1_001.fastq.gz RIP-Seq 780.0 MB
GSF-896-76-RIP-24June_S13_R1_001.fastq.gz RIP-Seq 780.0 MB
GSF-896-76-RIP-30Mar_S10_R1_001.fastq.gz RIP-Seq 782.0 MB
GSF-896-76-RIP-30Mar_S10_R1_001.fastq.gz RIP-Seq 782.0 MB
GSF-896-Adr-1-Input-24June_S5_R1_001.fastq.gz RIP-Seq 849.7 MB
GSF-896-Adr-1-Input-24June_S5_R1_001.fastq.gz RIP-Seq 849.7 MB
GSF-896-Adr-1-Input-30Mar_S2_R1_001.fastq.gz RIP-Seq 2.0 GB
GSF-896-Adr-1-Input-30Mar_S2_R1_001.fastq.gz RIP-Seq 2.0 GB
GSF-896-Adr-1-RIP-24June_S14_R1_001.fastq.gz RIP-Seq 785.4 MB
GSF-896-Adr-1-RIP-24June_S14_R1_001.fastq.gz RIP-Seq 785.4 MB
GSF-896-Adr1-RIP-30Mar_S11_R1_001.fastq.gz RIP-Seq 783.8 MB
GSF-896-Adr1-RIP-30Mar_S11_R1_001.fastq.gz RIP-Seq 783.8 MB
N2_E_15_12_16_CGATGT.fastq.gz RNA-Seq 1.3 GB
N2_E_15_12_16_CGATGT.fastq.gz RNA-Seq 1.3 GB
N2_E_15_9_16_CGATGT.fastq.gz RNA-Seq 1.2 GB
N2_E_15_9_16_CGATGT.fastq.gz RNA-Seq 1.2 GB
N2_embryo_111216_TAGCTT.fastq.gz RNA-Seq 1.3 GB
N2_embryo_111216_TAGCTT.fastq.gz RNA-Seq 1.3 GB
N2_embryo_230816_ATCACG.fastq.gz RNA-Seq 1.1 GB
N2_embryo_230816_ATCACG.fastq.gz RNA-Seq 1.1 GB
N2_L4_18_9_16_ATCACG.fastq.gz RNA-Seq 1.1 GB
N2_L4_18_9_16_ATCACG.fastq.gz RNA-Seq 1.1 GB
N2_L4_220816_ATCACG.fastq.gz RNA-Seq 1.2 GB
N2_L4_220816_ATCACG.fastq.gz RNA-Seq 1.2 GB
N2_L4_AYYA_TTAGGC.fastq.gz RNA-Seq 1.1 GB
N2_L4_AYYA_TTAGGC.fastq.gz RNA-Seq 1.1 GB
RB886_E_11_9_16_ACAGTG.fastq.gz RNA-Seq 1.2 GB
RB886_E_11_9_16_ACAGTG.fastq.gz RNA-Seq 1.2 GB
RB886_E_15_12_16_TTAGGC.fastq.gz RNA-Seq 1.2 GB
RB886_E_15_12_16_TTAGGC.fastq.gz RNA-Seq 1.2 GB
RB886_embryo_110916_CGATGT.fastq.gz RNA-Seq 1.2 GB
RB886_embryo_110916_CGATGT.fastq.gz RNA-Seq 1.2 GB
RB886_L4_160816_TGACCA.fastq.gz RNA-Seq 1.2 GB
RB886_L4_160816_TGACCA.fastq.gz RNA-Seq 1.2 GB
RB886_L4_20_9_16_TGACCA.fastq.gz RNA-Seq 1.2 GB
RB886_L4_20_9_16_TGACCA.fastq.gz RNA-Seq 1.2 GB
RB886_L4_Ayya_GCCAAT.fastq.gz RNA-Seq 1.1 GB
RB886_L4_Ayya_GCCAAT.fastq.gz RNA-Seq 1.1 GB

Analysis Pipelines (1)

geo_data_processing GSE110701