Mechanisms of Selenoprotein P translation regulation by long noncoding RNA

Abstract

Selenium (Se) is one of the essential trace elements in the body. Se is present in proteins in the form of selenocysteine (Sec), in which the sulfur of cysteine (Cys) is replaced by Se. These proteins are referred to as selenoproteins. There are 25 selenoproteins in the human genome, and they play important roles in various physiological functions, including as an antioxidant and in the synthesis of thyroid hormones. Sec is inserted into selenoproteins using the Sec insertion sequence (SECIS), which is located in the 3′ untranslated region. We have identified an antisense long noncoding RNA, CCDC152, which binds mRNA of selenoprotein P (SELENOP), one of the plasma selenoproteins. CCDC152 inhibits the binding of SECIS binding protein 2 (SBP2), which is a key protein for selenoprotein translation, to SECIS by direct interaction with SELENOP mRNA. Inhibiting the formation of the SBP2 and SECIS complex by CCDC152 reduces the binding of ribosomes to SELENOP mRNA and suppresses the translation step of SELENOP. As a result, CCDC152 causes a decrease in SELENOP protein levels independent of SELENOP mRNA levels. No impact was observed on the protein and mRNA expression levels of other selenoproteins. This review describes the mechanism of SELENOP protein suppression by CCDC152.

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