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

Nabeel S Ganem, Noa Ben-Asher, Aidan C Manning, Sarah N Deffit, Michael C Washburn, Emily C Wheeler, Gene W Yeo, Orna Ben-Naim Zgayer, Einav Mantsur, Heather A Hundley, Ayelet T Lamm

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

PubMed ↗ DOI ↗ PMC full text ↗

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.

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_2_051216_TTAGGC.fastq.gz RNA-Seq 1.3 GB
BB19_embryo_310816_TTAGGC.fastq.gz RNA-Seq 1016.1 MB
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_Ayya_GGCTAC.fastq.gz RNA-Seq 1.2 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_L4_221216_ACAGTG.fastq.gz RNA-Seq 1.3 GB
BB2_L4_230816_CAGATC.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_embryo_011216_TAGCTT.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_160816_GATCAG.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-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-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-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-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-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-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_9_16_CGATGT.fastq.gz RNA-Seq 1.2 GB
N2_embryo_111216_TAGCTT.fastq.gz RNA-Seq 1.3 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_220816_ATCACG.fastq.gz RNA-Seq 1.2 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_15_12_16_TTAGGC.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_20_9_16_TGACCA.fastq.gz RNA-Seq 1.2 GB
RB886_L4_Ayya_GCCAAT.fastq.gz RNA-Seq 1.1 GB
SRR6739731_GSM3014729 RNA-Seq 1.4 GB
SRR6739732_GSM3014730 RNA-Seq 1.3 GB
SRR6739733_GSM3014731 RNA-Seq 1016.0 MB
SRR6739734_GSM3014732 RNA-Seq 1.3 GB
SRR6739735_GSM3014733 RNA-Seq 1.3 GB
SRR6739736_GSM3014734 RNA-Seq 1.2 GB
SRR6739737_GSM3014735 RNA-Seq 1.2 GB
SRR6739738_GSM3014736 RNA-Seq 1.2 GB
SRR6739739_GSM3014737 RNA-Seq 1.3 GB
SRR6739740_GSM3014738 RNA-Seq 1.1 GB
SRR6739741_GSM3014739 RNA-Seq 1.1 GB
SRR6739742_GSM3014740 RNA-Seq 1.2 GB
SRR6739743_GSM3014741 RNA-Seq 1.3 GB
SRR6739744_GSM3014742 RNA-Seq 1.3 GB
SRR6739745_GSM3014743 RNA-Seq 1.1 GB
SRR6739746_GSM3014744 RNA-Seq 1.3 GB
SRR6739747_GSM3014745 RNA-Seq 1.3 GB
SRR6739748_GSM3014746 RNA-Seq 1.3 GB
SRR6739749_GSM3014747 RNA-Seq 1.2 GB
SRR6739750_GSM3014748 RNA-Seq 1.3 GB
SRR6739751_GSM3014749 RNA-Seq 1.1 GB
SRR6739752_GSM3014750 RNA-Seq 1.1 GB
SRR6739753_GSM3014751 RNA-Seq 1.2 GB
SRR6739754_GSM3014752 RNA-Seq 1.1 GB
SRR6739755_GSM3014753 RNA-Seq 1.2 GB
SRR6739756_GSM3014754 RNA-Seq 1.2 GB
SRR6739757_GSM3014755 RNA-Seq 1.2 GB
SRR6739758_GSM3014756 RNA-Seq 1.2 GB
SRR6739759_GSM3014757 RNA-Seq 1.2 GB
SRR6739760_GSM3014758 RNA-Seq 1.1 GB
SRR6739761_GSM3014759 RIP-Seq 1009.0 MB
SRR6739762_GSM3014760 RIP-Seq 1.8 GB
SRR6739763_GSM3014761 RIP-Seq 760.0 MB
SRR6739764_GSM3014762 RIP-Seq 792.0 MB
SRR6739765_GSM3014763 RIP-Seq 955.0 MB
SRR6739766_GSM3014764 RIP-Seq 1.7 GB
SRR6739767_GSM3014765 RIP-Seq 780.0 MB
SRR6739768_GSM3014766 RIP-Seq 781.0 MB
SRR6739769_GSM3014767 RIP-Seq 849.0 MB
SRR6739770_GSM3014768 RIP-Seq 2.0 GB
SRR6739771_GSM3014769 RIP-Seq 785.0 MB
SRR6739772_GSM3014770 RIP-Seq 783.0 MB

Potentially related datasets 1

These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.

Accession Source Title
GSE110701 GSE · GEO GEO ↗ Disruption in A-to-I editing levels affects C. elegans development more than a complete lack of editing

Analysis pipelines 1

Pipeline Assay Steps Dataset
GSE110701 Data Processing geo_data_processing — 7 GSE110701
Funding 3 grants
Grant Funder
P40 OD010440 NIH HHS (United States)
F32 GM119257 NIGMS NIH HHS (United States)
R01 GM130759 NIGMS NIH HHS (United States)