Roles of Zfp36l1 and Zfp36l1 in retinal development
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA666343 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12739300_1.fastq.gz | Fastqsanger.gz | |||
| SRR12739300_2.fastq.gz | Fastqsanger.gz | |||
| SRR12739400_1.fastq.gz | Fastqsanger.gz | |||
| SRR12739400_2.fastq.gz | Fastqsanger.gz | |||
| SRR12739301_1.fastq.gz | Fastqsanger.gz |
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Project description:ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved Adenylate-Uridylate-rich Elements (AREs) located in 3' untranslated regions (UTRs) to mediate RNA decay. We hypothesized that ZFP36L1 is a negative regulator of a post-transcriptional hub involved in the RNA half-life regulation of cancer-related transcripts. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo; whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wildtype and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells ± tet-on ZFP36L1, was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1, including HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3' UTRs of these targets for RNA degradation, thus suppressing their expression. Collectively, our findings reveal an indispensable role of ZFP36L1 as a post-transcriptional safeguard against aberrant hypoxic signaling and abnormal cell cycle progression.
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Project description:ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved Adenylate-Uridylate-rich Elements (AREs) located in 3' untranslated regions (UTRs) to mediate RNA decay. We hypothesized that ZFP36L1 is a negative regulator of a post-transcriptional hub involved in the RNA half-life regulation of cancer-related transcripts. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo; whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wildtype and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells ± tet-on ZFP36L1, was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1, including HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3' UTRs of these targets for RNA degradation, thus suppressing their expression. Collectively, our findings reveal an indispensable role of ZFP36L1 as a post-transcriptional safeguard against aberrant hypoxic signaling and abnormal cell cycle progression.
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Project description:We expressed either a wt or a phosphomutant version of ZFP36L1 in IMR90 ER:RAS cells. 7 days upon RAS induction (when the cells reach a fully senescent phenotype) we collected the RNA. ZFP36L1 is a RNA binding protein that binds to AU-rich elements in the 3âUTR of mRNAs and triggers their degradation. Our previous experiments showed that the activity of ZFP36L1 was key in the regulation of the senescent phenotype.By performing RNAseq we have uncovered the effect of expressing a constitutively active mutant of ZFP36L1 within the senescent transcriptome. 4 samples examined: Non-senescent cells (EV - 4OHT), Senescent cells (EV + 4OHT), Senescent cells expressing ZFP36L1wt and Senescent cells expressing ZFP36L1mut
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