To uncover this large collection of new genes, the Broad scientific team looked not at the RNA molecules themselves but at telltale signs in the DNA called chromatin modifications or epigenomic marks. They searched for genomic regions that have the same chromatin patterns as protein-coding genes, but do not encode proteins. By surveying the genomes of four different types of mouse cells (including embryonic stem cells and cells from various tissue types), they found an astounding 1,586 such loci that had not been previously described. The researchers also found that the vast majority of these genomic regions are transcribed into lincRNAs, and that these are conserved across mammals.
"The epigenomic marks revealed where these genes were hiding," said Mitch Guttman, a MIT graduate student working at the Broad Institute. "Analysis of their sequence then revealed that the genes are highly conserved in mammalian genomes, which strongly suggested that these genes play critical biological functions."
By correlating the expression patterns of lincRNAs in various cell types with the expression patterns of known critical protein-coding genes in those same cells, the scientists observed that lincRNAs likely play critical roles in helping to regulate a variety of different cellular processes, including cell proliferation, immune surveillance, maintenance of embryonic stem cell pluripotency, neuronal and muscle development, and gametogenesis. Further experimental evidence from several of the identified lincRNAs verified these observations.
Because of the stringent experimental conditions imposed by the researchers in identifying the 1,600 lincRNAs in the Nature study, it is likely that there are many more lincRNA genes hiding in plain sight in the genome, as well as other RNA-encoding genes that are as important to genome function as their better-recog
|Contact: Nicole Davis|
Broad Institute of MIT and Harvard