Identification of a novel endogenous long non-coding RNA that inhibits selenoprotein P translation

Yuichiro Mita, Risa Uchida, Sayuri Yasuhara, Kohei Kishi, Takayuki Hoshi, Yoshitaka Matsuo, Tadashi Yokooji, Yoshino Shirakawa, Takashi Toyama, Yasuomi Urano, Toshifumi Inada, Noriko Noguchi, Yoshiro Saito

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)6893-6907
Number of pages15
JournalNucleic acids research
Volume49
Issue number12
DOIs
Publication statusPublished - 2021 Jul 9

ASJC Scopus subject areas

  • Genetics

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