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New Research Provides Greater Insight into Gene Regulation

NEW YORK (GenomeWeb News) – Seven articles published in Science this week offer an overview of different ways that researchers are tackling the complexities of gene regulation.
The journal, published online today, includes a special section on gene regulation that provides a peek into the current state of research in the area, including everything from chromosome organization to transcription factors to various RNA regulators and riboswitches.
In the first article, Columbia University biochemist Oliver Hobert compares and contrasts transcription factor- and miRNA- mediated regulation of gene expression. As Hobert discusses, these regulators share many traits, such as cell type specificity, dependence on binding site accessibility, and influence over multiple genes.
But, he notes, there are important differences between them as well. For instance, miRNAs offer fast and reversible control of gene expression. In addition, they seem to have greater redundancy and can participate in more specialized — even compartmentalized — control of gene expression.
Next, senior author John Mattick, a molecular biologist at the University of Queensland, and his colleagues tackle the broader subject of non-protein-coding RNAs. They discuss the advent of research into these ncRNAs and review what is now known about the molecules’ influence over genome dynamics, cell biology, and development.
The article touches on the role of ncRNA in functional organization in the cell — for instance in chromatin architecture and nuclear organization. It also discusses genetic regulation by ncRNAs, particularly miRNAs and its evolutionary function.
“Given the functional versatility of RNAs, it is plausible that ncRNAs have represented a rich substrate for evolutionary innovations in eukaryotes,” the authors wrote. “[R]egulatory RNAs are centrally involved in the ontogeny of many organisms, from unique developmental pathways in protozoa to the control of conserved or clade-specific developmental regulators in multicellular animals.”
In the third article, Eugene Makeyev and Tom Maniatis, both molecular and cellular biologists at Harvard University, focus on the multilevel regulation by miRNAs. They describe the latest understanding of miRNA-regulated gene expression — including their cell and tissue-specific influence on transcription, alternative pre-mRNA splicing, and translation — and the implications of these for gene regulatory networks.
The authors conclude that some miRNAs may “prevent interference between spatially and temporally adjacent gene expression programs” by “rewiring the cell-specific networks at all levels of the regulatory hierarchy.”
Cornell University molecular biologists Leighton Core and John Lis turn their attention to another player in gene expression — RNA polymerase II. Their article reviews recent evidence in Drosophila and mammals suggesting the enzyme pauses near the promoter of many genes during the early elongation stage of transcription, providing additional gene regulation.
“Future investigations should focus on determining how promoter-specific binding proteins affect the transition between initiation and pausing, as well as the transition between pausing and productive elongation,” Core and Lis wrote. “[T]he results will provide important insights into the role of cell signaling events in the mechanics of transcription regulation.”
Next up, Job Dekker, a University of Massachusetts researcher who studies three-dimensional genome organization, discusses the importance of spatial chromosome organization in gene regulation. For instance, he describes how expression can be controlled via spatial gene clusters and their interactions with relatively distant regulatory elements, such as enhancers and repressors.
Meanwhile, Yale University biochemist Ronald Breaker describes so-called riboswitches, small, seemingly primitive RNA molecules that influence gene expression by interacting with molecules on mRNA. Despite their simple nature, Breaker reveals, these riboswitches have important and diverse functions. For instance, they can stabilize certain forms of mRNA, act in feedback loops that shut off certain genes when their products are no longer needed, and mediate some mRNA splicing events.
Finally, senior author Alexander Johnson, a microbiologist at the University of California at San Francisco, and his colleagues discuss the ways that eukaryotic transcription circuits evolve over time and how these changes affect a species’ morphology and physiology.