Cells Read DNA Backward and Forward: Direction is the Key

Cells read their own DNA, copying strands as they replicate. Now, scientists have discovered the mechanism that allows them to read it in the correct direction and prevents them from copying "junk DNA," which makes up long stretches of our genome.

A surprising amount of junk DNA gets copied into RNA, the molecule that carries DNA's messages to the rest of the cell. In fact, scientists have tried to figure out for years exactly what this RNA might be doing--if anything. In 2008, researchers actually discovered that much of this RNA is generated through a process called divergent expression, through which cells read their DNA in both directions moving away from a given starting point. Now, scientists have taken a closer look at divergent expression.

In order to study this mechanism a bit more closely, the researchers sequenced the messenger RNA (mRNA) of mouse embryonic stem cells.  Genetic information, controlled by DNA, is actually copied, or transcribed, into mRNA.

How is mRNA built? When the DNA double helix unwinds to reveal these genetic messages, RNA transcription can proceed in either direction. The copying begins when an enzyme called RNA polymerase latches onto the DNA at a spot known as the promoter. The RNA polymerase then moves along the strand, building the mRNA chain as it goes.

Eventually, the RNA polymerase reaches a stop signal at the end of the gene, which halts transcription and adds a sequence of bases known as a poly-A tail to the mRNA. This poly-A tail consists of a long string of the genetic base adenine. Known as polyadenylation, this process helps to prepare the mRNA molecule to be exported from the cell's nucleus.

In the end, the scientists found that polyadenylation also plays a major role in halting the transcription of upstream, noncoding DNA sequences. These regions have a high density of signal sequences for polyadenylation, which prompts enzymes to chop up the RNA before it gets very long. Stretches of DNA that code for genes have a low density of these signal sequences.

Currently, the scientists are still researching this upstream noncoding DNA, but the study does reveal how cells can read in both directions. It shows how cells initiate but then halt the copying of RNA in the upstream, or non-protein-coding direction, while allowing it to continue in the direction in which genes are correctly read.

"This is part of an RNA revolution where we're seeing different RNAs and new RNAs that we hadn't suspected were present in cells, and trying to understand what role they have in the health of the cell or the viability of the cell," said Phillip Sharp, one of the MIT researchers who worked on the study, in a news release. "It gives us a whole new appreciation of the balance of the fundamental processes that allow cells to function."

The findings are published in the journal Nature.