Combinatorial analysis of translation dynamics reveals eIF2 dependence of translation initiation at near-cognate codons.
Nucleic Acids Res
; 49(13): 7298-7317, 2021 07 21.
Article
em En
| MEDLINE
| ID: mdl-34226921
ABSTRACT
Although ribosome-profiling and translation initiation sequencing (TI-seq) analyses have identified many noncanonical initiation codons, the precise detection of translation initiation sites (TISs) remains a challenge, mainly because of experimental artifacts of such analyses. Here, we describe a new method, TISCA (TIS detection by translation Complex Analysis), for the accurate identification of TISs. TISCA proved to be more reliable for TIS detection compared with existing tools, and it identified a substantial number of near-cognate codons in Kozak-like sequence contexts. Analysis of proteomics data revealed the presence of methionine at the NH2-terminus of most proteins derived from near-cognate initiation codons. Although eukaryotic initiation factor 2 (eIF2), eIF2A and eIF2D have previously been shown to contribute to translation initiation at near-cognate codons, we found that most noncanonical initiation events are most probably dependent on eIF2, consistent with the initial amino acid being methionine. Comprehensive identification of TISs by TISCA should facilitate characterization of the mechanism of noncanonical initiation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Iniciação Traducional da Cadeia Peptídica
/
Fator de Iniciação 2 em Eucariotos
/
Códon de Iniciação
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article