%0 Journal Article
%T Regulation of cardiac microRNAs by serum response factor
%A Xiaomin Zhang
%A Gohar Azhar
%A Scott A Helms
%A Jeanne Y Wei
%J Journal of Biomedical Science
%D 2011
%I BioMed Central
%R 10.1186/1423-0127-18-15
%X MicroRNAs (miRNAs) are short (20 to 23-nucleotide), endogenous, single-stranded RNA molecules that regulate gene expression by hybridization to messenger RNAs (mRNAs) with the consequence of mRNA degradation or translational inhibition of targeted transcripts. Genes that encode for miRNA are transcribed by either RNA polymerase II or RNA polymerase III into primary miRNA (pri-miRNA) transcripts, which are then cleaved by the nuclear microprocessor complex formed by the RNase III enzyme Drosha (RNASEN) and the DGCR8 (DiGeorge critical region 8) protein. The RNase III Dicer cleaves off the loop of the pre-miRNA to generate a roughly 22-nucleotide miRNA duplex [1].Although insights into the regulatory function of miRNAs toward their mRNA targets are beginning to emerge, less is known about the regulation of miRNA gene expression and miRNA biogenesis [1]. For instance, it has been shown that miRNAs participate in the control of cardiac development, and a number of miRNAs play a role in cardiac hypertrophy [2-5]. In addition, serum response factor (SRF), an important transcription factor, participates in the regulation of several cardiac enriched miRNAs, including mir-1 and mir-133a [4,6]. However, it is unclear at what specific stage SRF regulates the biogenesis of miRNA.SRF is a member of the MADS (MCM1, agamous, deficiens, SRF) family of transcriptional activators that has been implicated in the regulation of a number of genes that are important in cell proliferation and differentiation. SRF regulates its target genes by binding to the serum response element (SRE), which contains a consensus CC(A/T6)GG (CArG) motif [7-9]. This cognate response site of SRF is found in the promoter region of certain immediate-early genes and many muscle-specific genes [9-11]. Two CArG-like elements have been found in the promoter of mir-1-1 and mir-1-2 genes [4]. The level of SRF expression apparently changes during development and adult aging [12]. Therefore, it is plausible that SRF m
%U http://www.jbiomedsci.com/content/18/1/15