“The manuscript primarily describes a new discovery, that cells contain specific sites where mRNAs can go to be destroyed.”

This manuscript is highly cited because it provides a new way of thinking about the metabolism of mRNAs in the cytoplasm and it also provided evidence that mRNAs were being targeted to specific sites—referred to as P-bodies  (view image)—for mRNA degradation and/or translation repression.

A second reason this manuscript gets cited frequently is that additional work rapidly demonstrated that P-bodies could be involved in other forms of regulating mRNA function, including translation repression and mRNA storage, control of mRNAs by miRNAs, and the cellular stress response. These connections led to the work being of interest to a wider scientific community.

The manuscript primarily describes a new discovery, that cells contain specific sites where mRNAs can go to be destroyed. However, this discovery, in combination with other pre-existing observations in the literature, led to the new intellectual synthesis of how cells control cytoplasmic mRNA metabolism, wherein mRNAs move between different biochemical and physically separated states for either translation, storage, or mRNA degradation.

Cells have to regulate their genes in many ways in order to be able to faithfully express the set of genes needed in a given situation. One important aspect of that control is the rate at which mRNAs are translated into protein, or are destroyed to allow new mRNAs to be used. This paper shows that cells contain special sites within them where mRNAs can be sent to either be stored or degraded, essentially a storage bin with a garbage disposal. This allows the cell to control which mRNAs it contains by controlling the transport of mRNAs into these structures.

My lab had been interested in understanding how eukaryotic cells degrade mRNAs in the cytoplasm and how that process is controlled. As we identified proteins involved in this process, we noticed that some of them were similar to proteins known to be in maternal mRNA storage granules—large RNA-proteins aggregates that store mRNAs in eggs for translation after fertilization.

This led Ujwal Sheth, a graduate student in the lab, to look at where these proteins were in somatic cells, and she used yeast cells as a model system. In these experiments she first observed the P-bodies and then went on to study their function. P-bodies have now been described in many different eukaryotic cells including human cells.