Whether you’re talking about real estate or miRNA expression, the phrase “location, location, location” expresses the undeniable importance of surroundings. Like protein-coding genes, miRNA genes can be turned on or off depending on the cellular context.
However, mechanisms responsible for cell-specific miRNA expression are largely unknown because miRNA promoters are not as well characterized as their protein-coding-gene counterparts. To study the transcriptional control of a pancreatic islet-specific miRNA gene, researchers in Israel characterized the promoter of pri-miR-375, a gene that encodes an miRNA involved in islet cell development.
Although many miRNA genes are embedded in and appear to be co-transcribed with protein-coding genes, other miRNA genes, such as pri-miR-375, are autonomous units that are transcribed by RNA polymerase II, capped, and polyadenylated to yield miRNA precursors (pri-mRNAs). These pri-MRNAs are sequentially processed by the RNases Drosha and Dicer into ~22-nt mature miRNAs.
The investigators identified an evolutionarily conserved 768-bp region of DNA upstream of the pri-miR-375 gene and linked this sequence to GFP and luciferase reporter genes. The sequence directed pancreatic islet-selective GFP expression in transgenic mice. The pri-miR-375 promoter and transcription start site were characterized by deletion analysis, targeted mutagenesis, and 5’-RACE.
The study revealed several important cis-acting promoter elements, including a TATA sequence and several E-box elements that could bind beta-cell bHLH transcription factors. These results demonstrate that the cell-specific expression of miR-375 results, at least in part, from transcriptional regulation. Get all the details at PLoS One, April 2009.