ABSTRACT
In humans, approximately 1000 different miRs have been annotated, although experimental verification for most of them is still required. In mammals, miRs are predicted to directly regulate the expression of 50% of all protein-coding genes [9]. MiRs genes are located either in genomic regions distinct from known transcription units (intergenic), in the introns of annotated genes (intronic), or more rarely exonic [10]. Intergenic miRs can be monocistronic with their own promoter or polycistronic with several miRs transcribed as a cluster or primary transcripts with a shared promoter. Intronic miRs can be found as a single miR or as a cluster of several miRs and are thought to be transcribed from the same promoter as their host gene and processed from the introns of host gene transcripts [10]. Intronic miRs tend to be regulated by the same promoter as the host gene, resulting in a similar expression profile of the “host” transcript and the miR. Moreover, some mature miRs are transcribed from multiple genomic loci with different miR hairpins and, therefore, different miR* strands [11]. The majority of miR genes are transcribed by RNA polymerase II into primary miRNA transcripts [12] which are usually several kilobases long and consists of an imperfectly paired stem of ~33 bp with a terminal loop and flanking segments [13-15]. The transcription of the miR genes is regulated by transcription factors, which also control the expression of protein-coding genes, such as c-myc and p53, via binding to typical promoter sequences or by epigenetic alterations [16]. The pri-miRs bear a 7-methylguanylate cap at the 5′-end and a poly (A) tail at the 3′-end like mRNAs [16, 17]. The hairpin structure of the pri-miR is the substrate for two endonucleases from the RNase III enzyme family, Drosha and Dicer.
