Cell Production Room Commander

How do cells manage to rapidly adapt their growth to changing environmental conditions? A new study by a research team from Würzburg provides an answer to this question.

Whether single-celled organism or mammal, plankton or redwood: growth is a basic principle of all life on this earth. And the starting point for this growth is usually the cell: for this to happen, it must double its components and ingredients in a short time so that it can then divide and trigger growth.

The process behind this is complicated and has yet to be deciphered in great detail. Now, however, a research team from Würzburg has managed to identify a key mechanism in this process. Professors Utz Fischer from the Julius Maximilian University of Würzburg (JMU) Biocentre and Jörg Vogel from the Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI) present the results of their work in the latest issue of the journal Cell Reports.

Ribosomes deliver new proteins

“For cells to grow, they have to produce a lot of new proteins. This happens inside the cell in specialized factories called ribosomes,” says Utz Fischer, chair of biochemistry at JMU. Up to ten million ribosomes are dedicated to this task in each human cell. Thus, the cells devote a large part of their resources and their energy reserves not only to the production of proteins, but especially to the production and maintenance of the ribosomes themselves. It is believed that up to 50% of the cellular energy reserve is required for this, making ribosome production the “costliest” process in the cell.

Of course, the cell cannot afford to use up such amounts of energy and raw materials unnecessarily. Therefore, it constantly monitors its environment to ensure that enough nutrients and other growth stimuli are available at all times. As soon as the “supply situation” deteriorates, it stops growing and stops producing new ribosomes – but still retains a large enough supply of ribosomes to be able to grow again without delay in better times.

A signaling complex is the central command center

The central command post of this process is the so-called mTORC1 signaling complex, a kind of nutrient sensor of the cell. “All information about the availability of nutrients and other growth stimuli converges on this signaling complex,” explains Dr. Cornelius Schneider, joint scientific collaborator of the two research laboratories and first author of the now published study.

Based on this information, mTORC1 coordinates the cellular response to changing environmental conditions and controls the production of ribosomal proteins. As the researchers were able to show, it uses the help of another protein, which has the scientific name LARP1. “mTORC1 can influence the LARP1 protein in such a way that, in the event of a nutrient deficiency, it binds to a signal sequence located at the beginning of the mRNAs of all ribosomal proteins. This results in reduced protein production,” says Schneider. mRNAs are, metaphorically speaking, the transporters of protein patterns from the cell nucleus to the ribosomes.

A basic supply always remains

Although the production of ribosomal proteins is reduced to an absolute minimum, it is never completely stopped. “This means that the cell can at any time start producing large quantities of ribosomes again. This allows it to react extremely quickly to changing conditions and switch from growing to saving energy,” says Utz Fischer. In this way, it is possible for the cell to always maintain a certain base mRNA supply of ribosomal proteins, even under poor conditions.

This also corresponds to another finding: LARP1 itself and the signaling network around mTORC1 are dysregulated in different types of cancer, as they are at the center of the decision for or against cell growth.

Original publication

An unusual mode of basal translation adjusts cellular protein synthesis capacity to metabolic needs. Cornelius Schneider, Florian Erhard, Beyenech Binotti, Alexander Buchberger, Jörg Vogel, Utz Fischer. Cell Reports,