Exon-junction complex association with stalled ribosomes and slow translation-independent disassembly.
Nat Commun
; 15(1): 4209, 2024 May 17.
Article
en En
| MEDLINE
| ID: mdl-38760352
ABSTRACT
Exon junction complexes are deposited at exon-exon junctions during splicing. They are primarily known to activate non-sense mediated degradation of transcripts harbouring premature stop codons before the last intron. According to a popular model, exon-junction complexes accompany mRNAs to the cytoplasm where the first translating ribosome pushes them out. However, they are also removed by uncharacterized, translation-independent mechanisms. Little is known about kinetic and transcript specificity of these processes. Here we tag core subunits of exon-junction complexes with complementary split nanoluciferase fragments to obtain sensitive and quantitative assays for complex formation. Unexpectedly, exon-junction complexes form large stable mRNPs containing stalled ribosomes. Complex assembly and disassembly rates are determined after an arrest in transcription and/or translation. 85% of newly deposited exon-junction complexes are disassembled by a translation-dependent mechanism. However as this process is much faster than the translation-independent one, only 30% of the exon-junction complexes present in cells at steady state require translation for disassembly. Deep RNA sequencing shows a bias of exon-junction complex bound transcripts towards microtubule and centrosome coding ones and demonstrate that the lifetimes of exon-junction complexes are transcript-specific. This study provides a dynamic vision of exon-junction complexes and uncovers their unexpected stable association with ribosomes.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ribosomas
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Biosíntesis de Proteínas
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ARN Mensajero
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Exones
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
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CIENCIA
Año:
2024
Tipo del documento:
Article