This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: When a cell gets ready to divide, it shuts down its gene-reading machinery almost entirely. For decades, the mechanism behind that shutdown was only partially understood.
A new study co-led by Alarcón and Lilian Kabeche, associate professor of molecular biophysics and biochemistry at Yale School of Medicine, identifies a missing piece: an enzyme best known for tagging RNA molecules that turns out to be wired into the cell division machinery itself. The findings, recently published in Molecular Cell, may point toward new cancer therapies. "As cells prepare to divide, they rapidly shut down most gene reading, or transcription," says Claudio R.
Alarcón, associate professor of pharmacology at Yale School of Medicine. "At that point, the cell needs to focus on dividing." The enzyme at the center of the study is METTL3, which modifies RNA by attaching a small chemical tag. Scientists have long known these tags help determine whether messenger RNA (mRNA) molecules are stabilized, transported or broken down.
Alarcón's lab previously discovered that METTL3 not only affects the fate of mRNA molecules but also regulates how mRNA molecules are produced. It does this by tagging a small RNA called 7SK. "7SK is a scaffolding nuclear RNA that is very important to regulate transcription," says Alarcón, a member of the Yale Cancer Biology Institute and Yale Cancer Center.
"You can think of 7SK as a little sponge that sequesters transcription-elongating factors—traps them—so they can't promote transcription." Growth-stimulating factors activate METTL3 to tag 7SK, which opens the trap. A protein complex is released, and the cell's gene-reading machine gets the signal to promote mRNA transcription. The newly generated mRNA molecules will then be translated into the proteins required for cell growth.
The new paper shows this same chain reaction is triggered the moment a cell commits to division. An enzyme called CDK1 activates METTL3, which sets off the same cascade of events. However, in this case, the goal is to complete transcription and clear mRNA molecules from DNA, rather than make new proteins.
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