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Nucleic Acids Res ; 49(12): 6893-6907, 2021 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-34142161

RESUMEN

Selenoprotein P (SELENOP) is a major plasma selenoprotein that contains 10 Sec residues, which is encoded by the UGA stop codon. The mRNA for SELENOP has the unique property of containing two Sec insertion sequence (SECIS) elements, which is located in the 3' untranslated region (3'UTR). Here, we coincidentally identified a novel gene, CCDC152, by sequence analysis. This gene was located in the antisense region of the SELENOP gene, including the 3'UTR region in the genome. We demonstrated that this novel gene functioned as a long non-coding RNA (lncRNA) that decreased SELENOP protein levels via translational rather than transcriptional, regulation. We found that the CCDC152 RNA interacted specifically and directly with the SELENOP mRNA and inhibited its binding to the SECIS-binding protein 2, resulting in the decrease of ribosome binding. We termed this novel gene product lncRNA inhibitor of SELENOP translation (L-IST). Finally, we found that epigallocatechin gallate upregulated L-IST in vitro and in vivo, to suppress SELENOP protein levels. Here, we provide a new regulatory mechanism of SELENOP translation by an endogenous long antisense ncRNA.


Asunto(s)
Regulación de la Expresión Génica , Biosíntesis de Proteínas , ARN Largo no Codificante/metabolismo , Selenoproteína P/genética , Catequina/análogos & derivados , Catequina/farmacología , Línea Celular Tumoral , Regulación hacia Abajo , Humanos , ARN Largo no Codificante/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/antagonistas & inhibidores , Selenoproteína P/biosíntesis
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