A genome-wide CRISPR screen identifies HuR as a regulator of apoptosis induced by dsRNA and virus.
J Cell Sci
; 135(6)2022 03 15.
Article
em En
| MEDLINE
| ID: mdl-35112703
ABSTRACT
We performed an unbiased whole-genome CRISPR/Cas9 screen in A549 cells to identify potential regulators involved in cell death triggered by double-stranded RNA (dsRNA). Of several top candidate genes, we identified the RNA-binding gene ELAV like protein 1 (256529), which encodes the protein Hu antigen R (HuR). Depletion of HuR led to less cell death induced by dsRNA. HuR is mainly involved in apoptosis, and all of its RNA recognition motifs are essential for its pro-apoptotic function. We further showed that the HuR depletion had no influence on the mRNA level of the anti-apoptotic gene BCL2, but instead that HuR downregulates BCL2 translation in a cap-independent way. Polysome fractionation studies showed that HuR retarded the BCL2 mRNA in the non-translating pool of polysomes. Moreover, protection from dsRNA-induced apoptosis by HuR depletion required the presence of BCL2, indicating that the pro-apoptotic function of HuR is executed by suppressing BCL2. Consistent with this, HuR regulated apoptosis induced by infection of encephalomyocarditis or Semliki Forest virus. Collectively, our work identified a suite of proteins that regulate dsRNA-induced cell death, and elucidated the mechanism by which HuR acts as a pro-apoptotic factor.
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Base de dados:
MEDLINE
Assunto principal:
RNA de Cadeia Dupla
/
Proteína Semelhante a ELAV 1
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article