Identification of microRNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples.
MicroRNAs (miRNAs) are a class of small RNA molecules that are implicated in post-transcriptional regulation of gene expression during development. The discovery and understanding of miRNAs has revolutionized the traditional view of gene expression. Alport syndrome (AS) is an inherited disorder of type IV collagen, which most commonly leads to glomerulonephritis and kidney failure. Patients with AS inevitably reach end-stage renal disease and require renal replacement therapy, starting in young adulthood. In this study, Solexa sequencing was used to identify and quantitatively profile small RNAs from an AS family. We identified 30 known miRNAs that showed a significant change in expression between two individuals. Nineteen miRNAs were up-regulated and eleven were down-regulated. Forty-nine novel miRNAs showed significantly different levels of expression between two individuals. Gene target predictions for the miRNAs revealed that high ranking target genes were implicated in cell, cell part and cellular process categories. The purine metabolism pathway and mitogen-activated protein kinase (MAPK) signaling pathway were enriched by the largest number of target genes. These results strengthen the notion that miRNAs and their target genes are involved in AS and the data advance our understanding of miRNA function in the pathogenesis of AS.
Clinical Medical Research Center, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 518020, China; Department of Hemodialysis, the Third People's Hospital of Shenzhen, Shenzhen 518112, China; Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang 424023, China.
Wen-biao
WB
Chen
Jian-rong
JR
Huang
Xiang-qi
XQ
Yu
Xiao-cong
XC
Lin
Yong
Y
Dai
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D024141:Collagen Type IV / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015723:Gene Library; D063990:Gene Ontology; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D010375:Pedigree; D022821:RNA Splice Sites; D055815:Young Adult
C478159:COL4A5 protein, human; D024141:Collagen Type IV; D035683:MicroRNAs; D022821:RNA Splice Sites
Alport syndrome; Gene Ontology; Induced pluripotent stem cells (iPSCs); Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway; Solexa sequencing; miRNA