Direct analysis of ribosome targeting illuminates thousand-fold regulation of translation initiation.
Cell Syst
; 13(3): 256-264.e3, 2022 03 16.
Article
en En
| MEDLINE
| ID: mdl-35041803
ABSTRACT
Translational control shapes the proteome in normal and pathophysiological conditions. Current high-throughput approaches reveal large differences in mRNA-specific translation activity but cannot identify the causative mRNA features. We developed direct analysis of ribosome targeting (DART) and used it to dissect regulatory elements within 5' untranslated regions that confer 1,000-fold differences in ribosome recruitment in biochemically accessible cell lysates. Using DART, we determined a functional role for most alternative 5' UTR isoforms expressed in yeast, revealed a general mode of increased translation via direct binding to a core translation factor, and identified numerous translational control elements including C-rich silencers that are sufficient to repress translation both in vitro and in vivo. DART enables systematic assessment of the translational regulatory potential of 5' UTR variants, whether native or disease-associated, and will facilitate engineering of mRNAs for optimized protein production in various systems.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ribosomas
/
Biosíntesis de Proteínas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cell Syst
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos