Remember in biology class when you learned about DNA replication and transcription? You probably remember your teacher telling you that all RNA is made from DNA. While scientists suspected RNA could copy other RNAs, they thought it was just an anomaly of lower order organisms like yeast and worms.
University of Pittsburgh researchers collaborated with Helicos BioSciences for the discovery. Using single molecule sequencing technology, scientists identified short RNAs they believe are copied directly from other RNAs in human cells and tissues.
The new class of short RNA is less than 200 nucleotides long — and are generated by RNA-dependent RNA polymerase. This opens up new ways of understanding gene expression and a slew of scientific questions.
Bino John, a professor at Pitt School of Medicine says this new discovery indicates human cells can copy RNA from RNA.
"We have shown that human cells might be copying RNA on a large scale," John says. We completely missed these RNAs before, he adds. These RNAs are found on the terminal ends of messenger RNA, which is the RNA that codes proteins.
"All the genetic scans have missed the relationship of the diseases with these particular RNAs because nobody looked for it. This is a new pathway set of RNAs and this might lead to a new diagnostic or therapeutic. It opens new avenues of treatment," John says.
Helicos has single molecule sequencing and has a feature that let's them capture the information specific to these RNAs. It cuts artifacts that are associated with other technologies by eliminating amplification, John says.
You get a good representation of what is in the cell from the Helicos platform.
We have a few thousand short RNA. Think of them like TV brands. Each Sony brand is sold in thousands. In this case, these RNAs have thousands of different brands and each RNA brand comes in many numbers in one cell. The RNA does different things and has its own function. It's also produced in different numbers in our cells.
"The large quantities can either help or create problems for the cell. We need to figure out diseases associated with these RNA," John says. "We don't know what they are yet."
Harvard geneticist George Church says RNA-dependent RNA polymerase has been known for a while. "It seems to be a testimonial to sequence RNA with the minimum number of steps. This is a discovery and is probably the tip of some iceberg."
There are plenty of pieces of the genome to explain, Church says, so any explanation is welcome.
Clearly, the RNA population is complex.
"Certainly the micro RNA and RNAi have been a revolution. Technologically it has been significant. It opened peoples eyes again to looking at the genome as more than a collection of proteins. This paper can't do that. But it is another bit of evidence there's a lot more to the genome than the current collection of genes," Church says.
This discovery has pumped more interest in Helicos (or at least that's what the stocks say). After all, the investment bank Leerink Swann, crossed the company off the list of sequencing companies earlier this year — thinking Helicos was losing the race for the $1000 genome.
The race is still on.
In a statement, Patrice Milos, Chief Scientific Officer at Helicos says, “this study... reinforces the potential clinical advantages of our single molecule-sequencing platform.”
Helicos is the only company out there in the market with a single molecule sequencer. Competition is anticipated, with a number of companies expected to come into the space soon. Ultimately the price of the sequencing machines will determine how much of the market the companies can attract.
But the technology and quality of the sequencing machine must come first. And perhaps Helicos is carving a nice niche for itself by using its single molecule sequencing to detect this new class of RNA — molecules that might turn out to have significant clinical implications.
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