RNA as a proxy signal for context-specific biological activity

This 2015 Harvard/MIT rodent study was of long (more than 200 nucleotides) noncoding (non-protein coding) RNAs (ribonucleic acids). These are of interest because:

“Within the mammalian body, the largest repertoire and diversity of lncRNA genes outside the germ line occurs in the brain, where lncRNAs exhibit regional and cell-specific localization.

The expression patterns of lncRNAs may serve as a proxy signal for important, context-specific biological activity.”

The researchers explained what they could and couldn’t determine with current techniques and technologies:

“The whole-gene ablation method used here is often a first approach to determine the functionality of a locus.

Although each of these loci contains a lncRNA, it is important to consider that any observation resulting from this strategy could reflect the loss of any regulatory element in the deleted region.

The rate of lncRNA gene discovery has significantly outpaced our ability to evaluate both the physiological significance and function of these genes. It is difficult to predict whether the loss of any particular lncRNA locus will present a phenotype, but crucial information on the spatiotemporal dynamics of expression from each locus can provide significant direction and focus to downstream mechanistic studies by highlighting those loci most likely to have a physiological impact.

It is important to stress that no single method exists that can account for all possible mechanisms of action of a noncoding locus. Within these limits, the phenotypes observed after ablation of specific lncRNA loci confirm that expression of this class of noncoding RNAs can serve as a proxy signal to identify functional genomic loci with physiological relevance to disease and development, independent of whether this activity is directly ascribed to a functional lncRNA molecule.”

http://www.pnas.org/content/112/22/6855.full “Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain”


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