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Cell economics 101

Lining our intestines, cells use a business-like approach to process food....


Every time we swallow food, cells lining our intestines step up their activity dramatically. According to a new study out of the Weizmann Institute of Science, researchers report how these cells respond in a most economic fashion. Their work appears in the journal Science.

In business or engineering, to get production quickly underway means instant decision making. This could mean instantly throwing all resources into boosting production with existing equipment, or it could mean spending your resources to put new machinery into the plant. The latter decision might seem less efficient, but can sometimes speed things up. Dr. Shalev Itzkovitz and his team from the Weizmann's Molecular Cell Biology Department, discovered this is the method adopted by our intestinal lining.
Intestinal lining is a single layer of elongated cells. On one side, the cell surface comes into contact with food and absorbs nutrients. On the other side, the same cell comes into contact with the bloodstream where it releases those nutrients.

Scientists discovered that each side differs in its composition of mRNA, or messenger RNA, with about 30 percent of intestinal genes expressing mRNAs on either side of the same cell.

However, the two sides differ in their amount of protein making machines, known as ribosomes. The number of ribosomes on the food-facing side are double that of the bloodstream-facing side. As a result, production of proteins on the food-facing side is much more efficient.

The scientists observed that whenever food enters the bowels, cells in the intestinal lining immediately respond by increasing production of ribosomes on their food-facing side. Then the cell dispatches large numbers of mRNAs carrying the genetic code to make ribosomes, to their food-facing side as well. The food-facing side of the cell now becomes an intense production shop, generating food processing proteins.

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 take action generating new mRNA molecules from DNA. Making new proteins takes the cells about half an hour. Instead, they can increase production within minutes by moving mRNA molecules onto the side of the cell rich with ribosomes. This strategy enables cells to process food in a fast and efficient manner."

These findings may have added implications. Knowing now how the process works, it may be possible to investigate whether the failure of mRNAs to move within a cell - or balance between high and low production areas of a cell - may play a role in such diseases as colitis, Crohn's disease, or possibly even bowel cancer.

Abstract
Asymmetric mRNA localization facilitates efficient translation in cells such as neurons and fibroblasts. However, the extent and significance of mRNA polarization in epithelial tissues are unclear. Here, we used single molecule transcript imaging and subcellular transcriptomics to uncover global apical-basal intracellular polarization of mRNA in the mouse intestinal epithelium. The localization of mRNAs did not generally overlap protein localization. Instead, ribosomes were more abundant on the apical sides, and apical transcripts were consequently more efficiently translated. Refeeding of fasted mice elicited a basal to apical shift in polarization of mRNAs encoding ribosomal proteins, which was associated with a specific boost in their translation. This led to increased protein production, required for efficient nutrient absorption. These findings reveal a post-transcriptional regulatory mechanism involving dynamic polarization of mRNA and polarized translation.

Authors: Andreas E. Moor1, Matan Golan1, Efi E. Massasa1, Doron Lemze1, Tomer Weizman1, Rom Shenhav1, Shaked Baydatch1, Orel Mizra

The research team included Dr. Andreas E. Moor, Matan Golan, Efi E. Massasa, Dr. Doron Lemze, Tomer Weizman, Rom Shenhav and Shaked Baydatch of the Molecular Cell Biology Department; Orel Mizrahi , Roni Winkler and Dr. Noam Stern-Ginossar of the Molecular Genetics Department; and Ofra Golani of the Life Sciences Core Facilities Department.

Dr. Shalev Itzkovitz's research is supported by the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Rothschild Caesarea Foundation; the Cymerman - Jakubskind Prize; and the European Research Council. Dr. Itzkovitz is the incumbent of the Philip Harris and Gerald Ronson Career Development Chair.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.


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Sep 26, 2017   Fetal Timeline   Maternal Timeline   News   News Archive




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 a cell nuclei (blue).
Image Credit: Weizmann Institute of Science



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