Could lead to future discoveries in basic biology, gene expression, RNA viruses, and disease
November 4, 2016
Original link: http://www.kurzweilai.net/a-super-high-resolution-snapshot-of-rna-folding
This
matrix of the RNA folding pathway shows how the transcription length
and nucleotide positions change over time. (Nucleotide position is along
the x-axis; transcription length is along the y-axis.) Each pixel in
the matrix is a piece of information about the structure of the RNA
molecules. (credit: Northwestern University)
Northwestern University engineers have invented a tool to make a super-high-resolution representation of RNA folding as it is being synthesized. It could potentially lead to future discoveries in basic biology, gene expression, RNA viruses, and disease.
Made up of long chains of nucleotides, RNA is responsible for many tasks in the cellular environment, including making proteins, transporting amino acids, gene expression, and carrying messages between DNA and ribosomes. To accomplish all these tasks, RNA folds into complex structures — “one of the biggest, most essential pieces of biology that we know comparatively nothing about,” said Julius B. Lucks, Ph.D, an associate professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering.
RNA folding is an essential requirement to life, but is difficult to investigate because the process occurs rapidly and is extremely hard to measure. Existing technology to image RNA folding is very-low-resolution and can’t image RNA’s individual components rapidly enough to capture these processes.
A molecular microscope
Instead, Lucks’s technology combines two existing components: a next-generation sequencing technique, which is typically used for sequencing human genomes, and a chemistry technique to turn RNA structure measurements into big data.
“Instead of treating it like a genome sequencer, we’re treating it like a molecular microscope to get a massive snapshot,” Lucks said. The technique captures the RNA-folding pathway in a massive dataset. Lucks’s group then uses computational tools to mine and organize the data, which reveals points where the RNA folds and what happens after it folds.
From the structural information that they gather, the researchers can reconstruct a movie of the RNA folding process. The team plans to make the data-analysis component open source, so researchers anywhere can download and run the program.*
Lucks and his team have already used the technology to view the folding of a riboswitch, a segment of RNA that acts as a genetic “light switch” to turn protein expression on or off in response to a molecular signal, in this case fluoride.
Supported by the National Institutes of Health, the research was published online on October 31 in Nature Structural and Molecular Biology.
* The researchers say the technology can be applied to all questions pertaining to RNA, such as how it plays a role in disease. Several notable human diseases, including Ebola, hepatitis C, and measles, are caused by RNA viruses, which are viruses that have RNA as their genetic material. And just as misfolded proteins can cause diseases, such as Alzheimer’s and Parkinson’s, RNA misfolding could also play a role in human illnesses.
