How cells keep mRNAs from sticking together: sequence choices reduce RNA aggregation

The useful part

All RNA molecules have another, less appreciated property: they are naturally sticky. Cells contain many thousands of mRNA molecules crowded into a tiny space, yet their mRNAs do not routinely form the large aggregates that their physical properties would seem to favor. Now, researchers at Whitehead Institute have uncovered one way cells may have evolved to avoid these sticky situations.

How it works

• The researchers' findings were published in the Proceedings of the National Academy of Sciences on September 14.
• Researchers have detailed information about which mRNAs are present in an E.
• coli cell, how many copies of each are present, and what those molecules look like — making it possible to model the behavior of an entire collection of cellular mRNAs, known as the transcriptome.
• Todisco developed computer simulations that tracked individual mRNA molecules and predicted how they would behave at concentrations similar to those found inside a cell.
• Using RNA sequencing, the researchers identified which mRNAs were enriched in the aggregates and found that their properties closely matched the simulations.

What to take from it

If mRNA has such a strong physical tendency to associate with other RNA molecules, how have cells managed that problem? Longer mRNAs were particularly prone to joining these clusters. Their findings suggest that evolution has shaped mRNA sequences to reduce unwanted interactions with other mRNAs.

Example or evidence

• The researchers found part of the answer written into the genetic sequences themselves.
• DNA carries the instructions for building proteins using three-letter sequences called codons, each of which specifies an amino acid, one of the building blocks of proteins.
• The genetic code contains redundancy: most amino acids can be encoded by more than one codon.
• The researchers took advantage of that flexibility to computationally create alternative versions of E.

Details worth keeping

If the chemistry of RNA makes these interactions so favorable outside cells, Todisco wondered, why shouldn't the same thing happen inside them? To investigate, Todisco and colleagues focused on Escherichia coli, or E. coli, a bacterium whose biology has been extensively studied.

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