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

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.

Modulating bioactivities of primary ammonium-tagged antimicrobial aliphatic polycarbonates by varying length, sequence and hydrophobic side chain structure.

Cationic aliphatic polycarbonates bearing primary ammonium side chains have been developed with relatively high molecular weights and controlled macromolecular architectures. These polycarbonates exhibit reasonable antimicrobial activity against Gram-negative and Gram-positive bacteria. The prepared homopolymers could be effective against Gram-negative bacteria whose growth is usually inhibited by copolymers with hydrophobic comonomer units when quaternary ammonium salts (QAS) are used at the cationic side chains. A methoxyethyl (ME) side chain was explored as a comonomer unit for modulating biological activities, besides conventional hydrophobic side chains including ethyl and benzyl groups. In contrast to the ethyl side chain that increases both antimicrobial and hemolytic activities, the ME side chain serves to enhance the antimicrobial activity, but suppresses the hemolytic activity. This could be attributed to the unique characteristics of an aliphatic polycarbonate bearing a ME side chain: hemocompatibility, cell adhesion property, and selective interactions with proteins. The benefits of blood compatibility of the cationic aliphatic polycarbonates with the use of the primary ammonium side chains have been reported for the first time. The polycarbonate main chain is subjected to hydrolysis, which reduces the inherent cytotoxicity of polycations. This hydrolytic property is specific to these primary ammonium-tagged polycarbonates and could be an advantage over previously reported QAS-tagged antimicrobial polycarbonates.