Polarization Of mRNA Regulates Intestinal Epithelium Efficiency

Each time you swallow food, cells that line your intestines must step up their activity in a sudden and dramatic manner. In fact, they rise to the challenge in the most economic fashion, according to a new study by Weizmann Institute of Science researchers.

In economics or engineering, when one has to get production ramped-up rapidly, instant decisions are made. These might involve instantly throwing all ones resources into boosting production with existing equipment, or else first spending all those resources to equip the plant with proper machinery.

The latter might seem to be a less efficient production method but it can actually, in some cases speed things up considerably. Dr. Shalev Itzkovitz and his team in Weizmann’s Molecular Cell Biology Department discovered that this is just the method adopted in the lining of the intestinal wall.

Ribosomal Balance

This lining, known as the intestinal epithelium, is a single layer of elongated cells that come into contact with food on one narrow side, and with the bloodstream on the other. Thus they absorb nutrients on one side and release them into the blood on the other.

The scientists discovered that the two sides of the cell differ in the composition of messenger RNA, or mRNA.

About 30 percent of the genes expressed in the intestines produced mRNAs that appeared either on one side of the cell or on the other. The two sides were also found to differ in the content of protein-making machines called ribosomes.

The number of ribosomes on the food-facing side was double that of the bloodstream-facing side; as a result, the production of proteins on that side was much more efficient.

instestinal espithelium

A circular organoid, about 0.5 mm in diameter, that mimics a cross-section of the gut in the test tube. In its outer layer, messenger RNA molecules of two different genes (red and green) are located on different sides of the cell nuclei (blue).
Credit: Weizmann Institute of Science

The scientists also discovered that whenever food enters the bowels, cells in the intestinal lining immediately respond by increasing the production of ribosomes, particularly in the food-facing part of the cell.

To this end, the cell dispatches to the food-facing area large numbers of mRNAs that carry the genetic code for making ribosomes. This part of the cell then becomes an intensive production shop of sorts, generating the proteins needed for processing the food.

Cellular Economics

Itzkovitz explains:

“For most of the night and day, cells in the lining of the intestines just loll around, but once food appears, they must instantly step into action. Generating new mRNA molecules from DNA in order to make new proteins would have taken the cells about half an hour.

Instead, they can increase production of certain proteins within minutes by moving the mRNA molecules encoding the relevant proteins into the side of the cell that is rich with ribosomes. This strategy enables them to deal with the arrival of food in a fast and efficient manner.”

In addition to opening the door to new studies in the “economics” of cells, the findings may have medical implications, as intestinal lining plays an important role in the both absorption of nutrients and protecting the body.

It may now be possible to investigate whether the failure of mRNAs to move to the proper part of the cell – or a lack of balance between mRNAs in the high- and low-production areas of the cell – may play a role in such diseases as colitis and Crohn’s disease, and possibly also in bowel cancer.

Andreas E. Moor, Matan Golan, Efi E. Massasa, Doron Lemze, Tomer Weizman, Rom Shenhav, Shaked Baydatch, Orel Mizrahi, Roni Winkler, Ofra Golani, Noam Stern-Ginossar, Shalev Itzkovitz
Global mRNA polarization regulates translation efficiency in the intestinal epithelium
Science 10 Aug 2017: eaan2399 DOI: 10.1126/science.aan2399

Top Image: Single-celled lining of the intestines under a microscope. Messenger RNA molecules of two different genes (red and green) are located on different sides of the cell nuclei (blue) Credit: Weizmann Institute of Science