Marking a significant technology breakthrough in tracking the interactions between RNA and DNA, scientists at the University of California have evolved a new technique.
Known as Mapping RNA Genome Interactions, the tool "MARGI" renders full data of the entire spectrum of RNA molecules that interact with segments of DNA in a single analysis.
The combination of RNA molecules with specific DNA sequences leads to regulated protein production within a cell. Thanks to MARGI, scientists can know in advance the scale of protein output and identify the gene script for modifications.
Knowing The Sequence
"Most of the human genome sequence is now known, but we still don't know what most of these sequences mean," said Sheng Zhong, the lead author of the study. Zhong is a professor of bioengineering at the UC San Diego Jacobs School of Engineering.
He hailed MARGI's utility in delivering a broad view of RNA molecules that combine with DNA and the sequences of their interactions.
The study has been published in Current Biology.
The existing methods are hampered by the limitation of having to focus on a single RNA molecule and failure of bulk analysis involving thousands of RNA-DNA pairs and RNA molecules. The new tool cuts that time frame for analysis from years to days. Thanks to MARGI bulk scanning of RNA-DNA interactions can be done in a few weeks.
How Does It Work?
In the analysis using MARGI, a mixture of sliced DNA and RNA is used wherein RNA molecules will interact with specific DNA pieces.
A unique linker entering the mixture will trigger RNA-DNA pair interactions. Later, a selective processing is attempted to bring them into chimeric sequences for deciphering the results.
The method's accuracy was also tested by the researchers as they looked for any false positive results. They analyzed it after mixing the RNA and DNA of fruit fly and human cells and picked up congenial pairs of RNA-DNA which were fully human or fully fruit fly and found that false pairs of half human and half fruit fly combined were a small fraction.
The entire mixture scanned by MARGI detected a large volume of true RNA-DNA interactions and the share of false pairs was just 2 percent.
One of the researchers, Bharat Sridhar, said the MARGI technique proved its efficacy though it is not fully perfect.
Messenger RNA And Proteins
Meanwhile, a new research result is forcing a relook into the number of three-letter sequences in messenger RNA triggering production of proteins.
The rule was that DNA transcribed into messenger RNA, which translates into proteins essential for biological functions with the core principle that only a small number of three-letter sequences in mRNA, called as "start codons," would enable protein production.
A relook on the rule looks inevitable after recent measurements from a team of scientists from the National Institute of Standards and Technology showed at least 47 start codons, each having the ability to instruct a cell to do protein synthesis exists. This is in contrast to the previous assumption that only seven of the 64 codons had the power to trigger the synthesis of proteins.
"It could be that many potential start codons had remained undiscovered because no one could see them," said lead author Ariel Hecht.
Represented by sequences of four letters — A, C, G, and T or U — genetic code corresponds to molecular units adenine, guanine, cytosine, and thymine (for DNA code) and uracil in the matter of RNA code.
