Bioinformatic analysis of the human DHRS4 gene cluster and a proposed mechanism for its transcriptional regulation.
BACKGROUND
The human DHRS4 gene cluster consists of three genes, DHRS4, DHRS4L2 and DHRS4L1. Among them, DHRS4 encodes NADP(H)-dependent retinol dehydrogenase/reductase. In a previous study, we investigated the alternative splicing of DHRS4 and DHRS4L2. DHRS4L1 was added to the gene cluster recently, but little is known about its structure and expression. To reveal the regulatory mechanism of the DHRS4 gene cluster expression, we studied the structure and transcription of DHRS4L1 in the context of the transcriptional behaviors of the human DHRS4 gene cluster. Based on the results of bioinformatics analysis, we propose a possible mechanism for the transcriptional regulation of the human DHRS4 gene cluster.


RESULTS
The homologous comparison analysis suggests that DHRS4, DHRS4L2 and DHRS4L1 are three homologous genes in human. DHRS4L1 and DHRS4L2 are paralogues of DHRS4, and DHRS4L2 is the most recent member of the DHRS4 gene cluster. In the minus strand of the human DHRS4 gene cluster, a gene transcribed in an antisense direction was found containing a 5' sequence overlapping the region of exon 1 and promoter of DHRS4. By cloning the full length of RNA variants through 5'RACE and 3'RACE, we identified two transcription start sites, within exon a2 and exon 1, of this newly named gene DHRS4L1 using neuroblastoma cell line BE(2)-M17. Analysis of exon composition in the transcripts of DHRS4 gene cluster revealed that exon 1 was absent in all the transcripts initiated from exon a1 of DHRS4L2 and exon a2 of DHRS4L1.


CONCLUSIONS
Alternatively spliced RNA variants are prevalent in the human DHRS4 gene cluster. Based on the analysis of gene transcripts and bioinformatic prediction, we propose here that antisense transcription may be involved in the transcriptional initiation regulation of DHRS4 and in the posttranscriptional splicing of DHRS4L2 and DRHS4L1 for the homologous identity of DHRS4 gene cluster. Beside the alternative transcriptional start sites, the antisense RNA is novel possible factor serving to remove exon 1 from the transcripts initiated from exon a1 and exon a2.
Su
Zhong-Jing
ZJ
Department of Cell Biology, Shantou University Medical College, Guangdong, China. g_zjsu@stu.edu.cn
Zhang
Qiao-Xia
QX
Liu
Ge-Fei
GF
Song
Xu-Hong
XH
Li
Qi
Q
Wang
Rui-Jian
RJ
Chen
Hai-Bin
HB
Xu
Xiao-Yuan
XY
Sui
Xu-Xia
XX
Huang
Dong-Yang
DY
D017398:Alternative Splicing; D045744:Cell Line, Tumor; D019295:Computational Biology; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D005810:Multigene Family; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D010088:Oxidoreductases; C539685:DHRS4 protein, human