July 12, 2013
Research Suggests RNA Stores More Functional Genome Data Than Previously Believed
redOrbit Staff & Wire Reports - Your Universe Online
Contrary to the belief that a large percentage of the human genome contains "junk" material, a team of Australian scientists report they have discovered an unexpectedly high proportion of functional elements that have been conserved through evolution.
According to Dr. Martin Smith and Professor John Mattick of the Garvan Institute of Medical Research in Sydney, less than 1.5 percent of the human genome is devoted to conventional genes (encodes for proteins). Other studies have shown between five and eight percent of the genome is conserved at the level of DNA sequence, indicating it is functional.
However, in a new study, Smith and Mattick compared the human genome to the genomes of 34 other mammals, including bats, mice, pigs, cows and dolphins. They discovered there is actually much more functional material stored at the level of RNA structure - perhaps as much as 30 percent. Their findings have been detailed in the open-access journal Nucleic Acids Research.
"DNA is a biological blueprint that must be copied into another form before it can be actualized," the Garvan Institute explained in a statement. "Through a process known as 'transcription', DNA is copied into RNA, some of which 'encodes' the proteins that carry out the biological tasks within our cells. Most RNA molecules do not code for protein, but instead perform regulatory functions, such as determining the ways in which genes are expressed.
"Like infinitesimally small Lego blocks, the nucleic acids that make up RNA connect to each other in very specific ways, which force RNA molecules to twist and loop into a variety of complicated 3D structures," they added.
Smith and Mattick developed a method to predict these complex RNA structures that is said to be more accurate to its predecessors. They applied it to the genomes of those nearly three-dozen animals, while also matching mutations within the genomes with consistent structures in the RNA - a combination which infers conserved function.
"Genomes accumulate mutations over time, some of which don't change the structure of associated RNAs. If the sequence changes during evolution, yet the RNA structure stays the same, then the principles of natural selection suggest that the structure is functional and is required for the organism," Dr. Smith explained.
"Our hypothesis is that structures conserved in RNA are like a common template for regulating gene expression in mammals - and that this could even be extrapolated to vertebrates and less complex organisms," he added. "We believe that RNA structures probably operate in a similar way to proteins, which are composed of structural domains that assemble together to give the protein a function."
Furthermore, the researchers suspect many RNA structures adopt specific molecules, including proteins or other RNAs, and help those molecules to bond with one another. Smith explains he and his colleagues hypothesize that non-coding RNAs "serve as scaffolds, tethering various complexes together, especially those that control genome organization and expression during development."
The researchers note they are aware that many RNA transcripts are linked with various diseases and developmental conditions, and that they are expressed differently in individual cells. They believe their structural predictions will be able to serve as a tool to help scientists better understand the function of these transcripts. The next step, according to Smith, is to conduct a closer analysis of the structures in order to determine exactly what they do inside of a cell, then to determine their relationships to both normal development and diseases.