Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function

Josipovic, Ivana1,7; Pflueger, Beatrice1,7; Fork, Christian1,7; Vasconez, Andrea E.1,7; Oo, James A.1,7; Hitzel, Juliane1,7; Seredinski, Sandra1; Gamen, Elisabetta2; zu Heringdorf, Dagmar Meyer3; Chen, Wei4,5,7; Looso, Mario6; Pullamsetti, Soni Savai2; Brandes, Ralf P.1,7; Leisegang, Matthias S.1,7

2018-03

10.1016/j.yjmcc.2018.01.015

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY   影响因子和分区

0022-2828

1095-8584

Sphingosine-1-Phosphate (S1P) is a potent signaling lipid. The effects of S1P are mediated by the five S1P receptors (S1PR). In the endothelium S1PR1 is the predominant receptor and thus S1PR1 abundance limits S1P signaling. Recently, lncRNAs were identified as a novel class of molecules regulating gene expression. Interestingly, the lncRNA NONHSAT004848 (LISPR1, Long intergenic noncoding RNA antisense to S1PR1), is closely positioned to the S1P1 receptors gene and in part shares its promoter region. We hypothesize that LISPR1 controls endothelial S1PR1 expression and thus S1P-induced signaling in endothelial cells. In vitro transcription and translation as well as coding potential assessment showed that LISPR1 is indeed noncoding. LISPR1 was localized in both cytoplasm and nucleus and harbored a PolyA tail at the 3'end. In human umbilical vein endothelial cells, as well as human lung tissue, qRT-PCR and RNA-Seq revealed high expression of LISPR1. S1PR1 and LISPR1 were downregulated in human pulmonary diseases such as COPD. LISPR1 but also S1PR1 were induced by inflammation, shear stress and statins. Knockdown of LISPR1 attenuated endothelial S1P-induced migration and spheroid outgrowth of endothelial cells. LISPR1 knockdown decreased S1PR1 expression, which was paralleled by an increase of the binding of the transcriptional repressor ZNF354C to the S1PR1 promoter and a reduction of the recruitment of RNA Polymerase II to the S1PR1 5'end. This resulted in attenuated S1PR1 expression and attenuated S1P downstream signaling. Collectively, the disease relevant lncRNA LISPR1 acts as a novel regulatory unit important for S1PR1 expression and endothelial cell function.

LncRNA S1P COPD Angiogenesis Epigenetics

SCI

英语

其他

German Research Foundation[DFG SFB 834 TP A2] ; German Research Foundation[SFB 1039 TP A1]

Cardiovascular System & Cardiology ; Cell Biology

Cardiac & Cardiovascular Systems ; Cell Biology

WOS:000428102200006

ELSEVIER SCI LTD

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Goethe Univ, Inst Cardiovasc Physiol, Frankfurt, Germany
2.Max Planck Inst Heart & Lung Res, Dept Lung Dev & Remodelling, Bad Nauheitn, Germany
3.Goethe Univ, Inst Gen Pharmacol & Toxicol, Frankfurt, Germany
4.Max Delbruck Ctr Mol Med, Lab Novel Sequencing Technol Funct & Med Genom, Berlin, Germany
5.Southern Univ Sci & Technol, Dept Biol, Shenzhen, Guangdong, Peoples R China
6.Max Planck Inst Heart & Lung Res, ECCPS Bioinformat Core Unit, Bad Nauheim, Germany
7.German Ctr Cardiovasc Res DZHK, Partner Site RheinMain, Frankfurt, Germany

Josipovic, Ivana,Pflueger, Beatrice,Fork, Christian,et al. Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2018,116:57-68.

Josipovic, Ivana.,Pflueger, Beatrice.,Fork, Christian.,Vasconez, Andrea E..,Oo, James A..,...&Leisegang, Matthias S..(2018).Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,116,57-68.

Josipovic, Ivana,et al."Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 116(2018):57-68.