Researchers find complexity of regulation by microRNA genes

Collaborating researchers at New York University and Rockefeller University have discovered that microRNA genes, which have recently been shown to have key roles in gene regulation, can team up and regulate target genes in mammals. MicroRNAs are a recently discovered large class of regulatory, non-coding genes, which bind to partially complementary sites in target messenger RNA to regulate their stability and translation. However, little has been known about the biological function of microRNAs–a process the current study sought to explore.

The paper, published in the latest issue of the journal Nature Genetics, found that a microRNA gene regulates, on average, 200 different human gene transcripts and that many microRNAs can coordinate their activities to regulate specific target genes. The paper contains detailed genome-wide predictions for all human microRNAs as well as tissue-specific predictions. Several predictions were validated experimentally. The findings demonstrate an unforeseen staggering complexity of gene regulation executed by microRNAs on a genome-wide level.

In this study, lead author Nikolaus Rajewsky, a genomics faculty member in NYU’s Center for Comparative Functional Genomics and an assistant professor in the Department of Biology, and the research team developed “PicTar,” a new algorithm for the identification of microRNA target sites in the genome and used it to compare sequences from eight different vertebrates.

“The study demonstrates that computational methods, in conjunction with the exploding amounts of available sequence data from different species, have the power to not only arrive at large-scale and yet specific, testable predictions for gene regulation, but also to produce new general insights into how gene regulation is organized in the genome,” says Rajewsky, who holds an affiliated appointment at NYU’s Courant Institute of Mathematical Sciences.

Rajewsky’s research program on bioinformatics predictions of regulatory elements in genomes is being conducted at NYU’s Center for Comparative Functional Genomics, where the focus of the research programs is to combine genomic approaches with developmental genetics and evolution to understand how changes in genomes give rise to the diversity of regulatory mechanisms in animals and plants.