C-3-16
RNA-Sequencing-Based Screening of Long Non-Coding
RNAs Targeted by Steroid and Xenobiotic Receptor
Kuniko Horie-Inoue 1

Kotaro Azuma 2khorie-tky@umin.ac.jp

kazum-tky@ umin.ac.jp

Kazuhiro Ikeda 1
ikeda@saitama-med.ac.jp

Satoshi Inoue 1.2
INOUE-GER@h.u-tokyo.ac.jp
1

Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka,Saitama 350-1241, Japan
Departments of 2 Geriatric Medicine and 3 Anti-Aging Medicine, Graduate School ofMedicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanKeywords: long non-coding RNA, steroid and xenobiotic receptor, osteoblast, RNA -sequencing
Steroid and xenobiotic receptor, SXR, is a nuclear receptor that plays an impor tant role in thedetoxification of bile acids and chemical compounds [1]. We have previously showed that vitamin
K 2 -liganded SXR is a transcriptional regulator of bone marker genes [2,3]. Recent advance ingenomic technology enables to identify numerous long non-coding RNAs (lncRNAs), which haveno obvious coding capacities with their length >200 bp and widely transcribed in spati otemporal
specific manners [4]. While biological functions of some lncRNAs have been characterized, few
lncRNAs have been identified in the context of nuclear receptor-regulated gene network.
Here we screened functional lncRNAs upregulated by SXR agonists in human osteoblastic
MG63 cells overexpressing SXR, based on RNA-sequencing analysis. Among RefSeq transcripts
with >1.5-fold up-regulation or < 0.67-fold down-regulation by either rifampicin or vitamin K 2
versus vehicle, ~10% were identified as NR non-coding transcripts and half of the NR transcripts
were up-regulated by either SXR ligand (except transcripts down-regulated by the other ligand).
Based on the recent genomic data, one third of the up-regulated NR transcripts were lncRNAs
except non-coding variants of coding-genes. Interestingly, known lncRNA HOTAIR [5] wasinvolved in the group of putative SXR target lncRNAs. We cons ider that this integrative screen oflncRNAs will reveal the RNA-mediated transcriptional regulation of SXR, and will provide useful
information for the potential use of lncRNAs as new osteoblastic biomarkers and therapeutictargets for bone diseases such as osteoporosis.
[1] Sonoda, J., Rosenfeld, J.M., Xu, L., Evans, R.M., and Xie, W., A nuclear receptor-mediatedxenobiotic response and its implication in drug metabolism and host protection , Current Drug
Metabolism, 4:59-72, 2003.
[2] Tabb, M.M., et al., Vitamin K2 regulation of bone homeostasis is mediated by the steroid andxenobiotic receptor SXR. Journal of Biological Chemistry, 278:43919-43927, 2003.
[3] Ichikawa, T., Horie-Inoue, K., Ikeda, K., Blumberg, B., and Inoue, S., Steroid and xenobiotic
receptor SXR mediates vitamin K2-activated transcription of extracellular matrix -related genes
and collagen accumulation in osteoblastic cells. Journal of Biological Chemistry,
281(25):16927-34, 2006.
[4] FANTOM consortium, The transcriptional landscape of t he mammalian genome, Science,
309:1559-1563, 2005.
[5] Rinn, J. L., et al., Functional demarcation of active and silent chromatin domains in human
HOX loci by noncoding RNAs, Cell, 129:1311-1323, 2007.