Control of mRNA splicing by noncoding intragenic RNA elements that evoke a cellular stress response.
Int J Biochem Cell Biol
; 105: 20-23, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30282053
ABSTRACT
Once activated by double-helical RNA, mammalian RNA-dependent stress protein kinase, PKR, phosphorylates its substrate, translation initiation factor eIF2α, to inhibit translation. eIF2α phosphorylation is critical for mounting a cellular stress response. We describe short, 100-200 nucleotide elements within cellular genes that, once transcribed, form RNA structures that potently activate PKR in the vicinity of the RNA and thereby tightly regulate gene expression in cis. Intragenic RNA activators of PKR can (a) attenuate translation of the encoded mRNA by activating PKR and inducing eIF2α phosphorylation, exemplified by the IFN-γ gene, or (b) greatly enhance mRNA splicing efficiency by activating PKR and inducing nuclear eIF2α phosphorylation, thus enabling efficient early spliceosome assembly, exemplified by the adult and fetal globin genes and the TNF-α gene that activates PKR through an RNA pseudoknot conserved from fish to humans. These opposite outcomes considerably extend the potential scope of gene regulation by these novel RNA elements.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Splicing de RNA
/
RNA não Traduzido
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article