U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

SRX24354548: GSM8228798: Zebrafish, Riboseq, low dose, uninj2; Danio rerio; OTHER
1 ILLUMINA (Illumina NovaSeq 6000) run: 40.2M spots, 12.1G bases, 3.9Gb downloads

External Id: GSM8228798_r1
Submitted by: Shandong University
Study: Double-stranded RNA triggers a distinct integrated stress response in the early embryo [RNA-seq, Ribo-seq]
show Abstracthide Abstract
Double-stranded RNA (dsRNA) is associated with virus infections and is present as by-products during the transcription of synthetic mRNA, which has been widely used in gene gain-of-function studies and serves as a core component in emerging mRNA-based therapies1-4. The presence of dsRNA in host cells induces an integrated stress response that functions to prevent virus replication and infection5,6. Unlike differentiated cells, undifferentiated cells adopt a distinct defense strategy against RNA virus infection7, but the mechanism is unclear. We show a previously unidentified response triggered by dsRNA in the early embryo. Although dsRNA causes a global protein translation inhibition in a PKR-eIF2a independent manner and leads to developmental delay and cell necrosis, it also strongly induces p53 activation, which then upregulates Interferon Stimulated Genes independently of interferon ligands. Importantly, we demonstrate that the burst of p53 signaling dose not result in cell death but functions as a protective mechanism against deleterious translation blockage by slowing down global protein degradation via ISGylation. Our work has identified a distinct dsRNA-induced stress response in the embryo, reflecting an ancient innate immune memory before the establishment of the IFN system. It also raises the provocative question as to the original protective role of p53 during evolution. Overall design: To characterize the distribution of ribosomes on mRNA, we performed Ribosome profiling (Ribo-seq) analysis with RNA-seq on dsRNA-injected embryos.
Sample: Zebrafish, Riboseq, low dose, uninj2
SAMN41071434 • SRS21112316 • All experiments • All runs
Organism: Danio rerio
Library:
Name: GSM8228798
Instrument: Illumina NovaSeq 6000
Strategy: OTHER
Source: TRANSCRIPTOMIC
Selection: other
Layout: PAIRED
Construction protocol: Both control group and dsRNA-injected embryos at 5 hpf were thoroughly lysed on ice using lysis buffer.The lysate was then centrifuged at 12000g at 4°C for 10 minutes to remove cellular components, including undigested material such as cell nuclei.Then, RNaseI was added to the supernatant and incubated at 25°C for 30 minutes to digest RNA, while the RNA fragments protected by ribosomes were preserved. Subsequently, an RNA inhibitor was added to terminate the digestion reaction. The lysate was subjected to sucrose density gradient centrifugation, and fractions containing single peaks at 260nm wavelength around the 80S monosome region were collected. The collected mixture was then thoroughly lysed using Trizol for RNA extraction. RNA fragments within the size range of 26-34nt was separated using polyacrylamide gel electrophoresis without RNase, and the corresponding bands were collected. The recovered bands were subjected to ligation reaction, where a preadenylylated and 3'-blocked linker (5' rApp-CTGTAGGCACCATCAAT-NH2 3') was attached to the 3' end of the RNA. The ligated products were then recovered by performing polyacrylamide gel electrophoresis. Subsequently, the recovered RNA fragments were reverse transcribed using a reverse primer to obtain extended cDNA molecules. The purified cDNA was subjected to circularization by using CircLigase (Epicentre, CL4111K), resulting in the formation of circular cDNA molecules. To remove residual rRNA components in the cDNA, a method involving hybridization with complementary primers specific to rRNA and subsequent heat denaturation was employed. The remaining circularized cDNA was then amplified through PCR, and barcode sequences were incorporated.
Runs: 1 run, 40.2M spots, 12.1G bases, 3.9Gb
Run# of Spots# of BasesSizePublished
SRR2879025640,172,24812.1G3.9Gb2024-04-26

ID:
32669204

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...