Genome-wide identification of long noncoding RNAs in rat models of cardiovascular and renal disease.
Long noncoding RNAs (lncRNAs) are an emerging class of genomic regulatory molecules reported in various species. In the rat, which is one of the major mammalian model organisms, discovery of lncRNAs on a genome-wide scale is lagging. Renal lncRNA sequencing and lncRNA transcriptome analysis were conducted in 3 rat strains that are widely used in cardiovascular and renal research: the Dahl salt-sensitive rat, the spontaneously hypertensive rat, and the Dahl salt-resistant rat. Through the RNA sequencing approach, 3273 transcripts were identified as rat lncRNAs. A majority of lncRNAs were without predicted target genes. Differential expression of 273 and 749 lncRNAs was detected between Dahl salt-sensitive versus Dahl salt-resistant and Dahl salt-sensitive versus spontaneously hypertensive rat comparisons, respectively. To couple the observed differential expression of lncRNAs with the status of mRNAs, an mRNA transcriptome analysis was conducted. Several cis mRNA genes were coregulated with lncRNAs. Of these, the protein expression status of 4 target genes, Asb3, Chac2, Pex11b, and Sp5, were differentially expressed between the relevant strain comparisons, thereby suggesting that the differentially expressed lncRNAs associated with these genes are candidate genetic determinants of blood pressure. This study serves as a first-generation catalog of rat lncRNAs and illustrates the prioritization of lncRNAs as candidates for complex polygenic traits.
From the Program in Physiological Genomics, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, OH.
Kathirvel
K
Gopalakrishnan
From the Program in Physiological Genomics, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, OH.
Sivarajan
S
Kumarasamy
From the Program in Physiological Genomics, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, OH.
Blair
B
Mell
From the Program in Physiological Genomics, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, OH. bina.joe@utoledo.edu.
Bina
B
Joe
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study / Q000379:methods*; D015151:Immunoblotting; D007674:Kidney Diseases / Q000175:diagnosis / Q000235:genetics*; D046228:Microarray Analysis; D062085:RNA, Long Noncoding / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
D062085:RNA, Long Noncoding
RNA untranslated; blood pressure; rats, inbred Dahl; rats, inbred SHR; transcriptome