Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 212, Issue 2, Pages 358-367Publisher
WILEY
DOI: 10.1002/jcp.21030
Keywords
-
Categories
Ask authors/readers for more resources
In cardiac cells, KCNQI assembles with KCNEI and forms a channel complex constituting the slow delayed rectifier current I-Ks. Expression of KCNQI and KCNEI are regionally heterogeneous and changes with pathological states of the heart. The aims of this study were to decipher the molecular mechanisms for transcriptional and post-transcriptional regulation expression of KCNQI and KCNEI genes and to shed light on the molecular mechanisms for their spatial heterogeneity of distribution. We cloned the 5'-flanking region and identified the transcription start sites of the KCNQI gene. We characterized the core promoters of KCNQI and KCNEI and revealed the stimulating protein (Sp 1) as a common transactivator of KCNQI and KCNEI by interacting with the Sp I cis-acting elements in the core promoter regions of these genes. We also characterized the 3' untranslated regions (3'UTRs) of the genes and experimentally established KCNQI and KCNEI as targets for repression by the muscle-specific microRNAs miR-133 and miR-1, respectively. We demonstrated spatial heterogeneity of KCNQI and KCNEI distributions at three axes (interventricular, transmural and apical-basal) and disparity between mRNA and protein expressions of these genes. We also found characteristic regional differences of expressions of SpI and miR-l/miR- 133 in the heart. Our study unraveled a novel aspect of the cellular function of miRNAs and suggests that the I-Ks-encoding genes KCNQI and KCNEI expressions are dynamically balanced by transcription factor regulation and miRNA repression. The heterogeneities of SpI and miR-I/miR-133 offer an explanation for the well-recognized regional differences and disparity between mRNA and protein expressions of KCNQI and KCNEI.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available