‘Don’t touch my junk DNA!’ says gene signal sequence

Scientists at MIT say they have discovered a mechanism that prevents noncoding DNA from being copied, by pointing the copying in the right direction.

Almost all of the human genome is made of noncoding, or "junk" DNA, that is, DNA that usually doesn't get copied and encoded into proteins.

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So when copying DNA, how do cells tell the diference between actual genes and non-coding DNA?

DNA replication begins at regions on the DNA molecule called promoters, sequences located at the beginning of genes that are to be copied. The enzyme that copies DNA, called RNA polymerase, latches on to the promoter and starts unzipping the DNA double helix, spooling out a chain of what will become messenger RNA mRNA for short that contains the information of the gene.

But how does the RNA polymerase know which direction to go? Until now, scientists didn't know. But in research published in the current issue of the scientific journal Nature,MIT biologists say they have discovered the mechanism that points transcription in the right direction.

In all living things except bacteria, the RNA polymerase continues unzipping the DNA until it reaches a stop signal, at which point it stops copying and begins adding a chain of adenine bases to the pre-mRNA molecule, usually a couple hundred links long. This "poly-A" tail protects the mRNA as it exits the nucleus and travels to the ribosome, where the molecule's information is synthesized into proteins.

By sequencing mRNA of mouse embryonic stem cells, the researchers found that the signal sequences for creating poly-A tails a process known as polyadenylation are also prevalent "upstream" from the promoter. An RNA polymerase that encounters these sequences will chop up its pre-mRNA. Sequences of DNA that are to be coded into genes, by contrast, have a low density ofpolyadenylation signal sequences.

The researchers also found that thepolyadenylation signal sequences are more likely to beignored when they appear within coding sequences, thanks to a tiny protein complex called U1 snRNP. WhenU1 snRNP binds to an RNA polymerase,polyadenylation is supressed. The researchers discovered that binding sites forU1 snRNP are more prevalent in coding sequences than noncoding ones.

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'Don't touch my junk DNA!' says gene signal sequence