Ribosome rescue factor PELOTA modulates translation start site choice for C/EBPα protein isoforms.
Life Sci Alliance
; 7(7)2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38803235
ABSTRACT
Translation initiation at alternative start sites can dynamically control the synthesis of two or more functionally distinct protein isoforms from a single mRNA. Alternate isoforms of the developmental transcription factor CCAAT/enhancer-binding protein α (C/EBPα) produced from different start sites exert opposing effects during myeloid cell development. This choice between alternative start sites depends on sequence features of the CEBPA transcript, including a regulatory uORF, but the molecular basis is not fully understood. Here, we identify the factors that affect C/EBPα isoform choice using a sensitive and quantitative two-color fluorescent reporter coupled with CRISPRi screening. Our screen uncovered a role of the ribosome rescue factor PELOTA (PELO) in promoting the expression of the longer C/EBPα isoform by directly removing inhibitory unrecycled ribosomes and through indirect effects mediated by the mechanistic target of rapamycin kinase. Our work uncovers further links between ribosome recycling and translation reinitiation that regulate a key transcription factor, with implications for normal hematopoiesis and leukemogenesis.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ribossomos
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Biossíntese de Proteínas
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Isoformas de Proteínas
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Proteína alfa Estimuladora de Ligação a CCAAT
Limite:
Animals
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Humans
Idioma:
En
Revista:
Life Sci Alliance
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos