title: A liver X receptor (LXR)-beta alternative splicing variant (LXRBSV) acts as an RNA co-activator of LXR-beta.
abstract: We report the isolation and functional characterization of a novel transcriptional co-activator, termed LXRBSV. LXRBSV is an alternative splicing variant of liver X receptor (LXR)-beta LXRBSV has an intronic sequence between exons 2 and 3 in the mouse LXR-beta gene. The LXRBSV gene is expressed in various tissues including the liver and brain. We sub-cloned LXRBSV into pSG5, a mammalian expression vector, and LXRBSV in pSG5 augmented human Sterol Response Element Binding Protein (SREBP)-1c promoter activity in HepG2 cells in a ligand (TO901317) dependent manner. The transactivation mediated by LXRBSV is selective for LXR-beta. The LXRBSV protein was deduced to be 64 amino acids in length; however, a GAL4-LXRBSV fusion protein was not able to induce transactivation. Serial deletion constructs of LXRBSV demonstrated that the intronic sequence inserted in LXRBSV is required for its transactivation activity. An ATG mutant of LXRBSV was able to induce transactivation as wild type. Furthermore, LXRBSV functions in the presence of cycloheximide. Taken together, we have concluded that LXRBSV acts as an RNA transcript not as a protein. In the current study, we have demonstrated for the first time that an alternative splicing variant of a nuclear receptor acts as an RNA co-activator.
authors.affiliation: Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan. khashi@med.gunma-u.ac.jp
authors.forename: Koshi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Emi
authors.initials: E
authors.lastname: Ishida
authors.forename: Shunichi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shibusawa
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Monden
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Satoh
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D006801:Humans; D007438:Introns / Q000235:genetics; D000071518:Liver X Receptors; D051379:Mice; D008969:Molecular Sequence Data; D057093:Orphan Nuclear Receptors / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger