The eIF4E factor reveals itself in a new way
Published on May 2, 2019
This discovery made by a team of IRIC Investigators could make its way into cell biology textbooks. The laboratory of Katherine L.B. Borden recently published a study in Cell Reports revealing a new role for the eIF4E factor: actively participating in the cleavage of the terminal end of messenger RNAs in order to accelerate their conversion to protein.
Before being used to produce a protein, the information contained in a gene first transits by way of a messenger RNA (mRNA). A multitude of proteins act as mentors for these mRNAs. As soon as they are created in the nucleus, they help them mature, leave the nucleus, and lead them to the ribosome where they will be read and translated into proteins.
The eIF4E factor is one of those proteins and helps approximately 3,500 different types of mRNAs accelerate their march to the ribosome.
To do so, the eIF4E factor modulates the translation of mRNAs by attaching itself to their cap, at the leading end of the mRNAs. It then acts in three ways to accelerate the movement of information: by increasing the translation rate of the mRNA, by increasing its stability in the cytoplasm, and by participating in its export from the nucleus. Katherine Borden’s team discovered a fourth mechanism, completely by chance.
While studying its mRNA export activity, the Borden laboratory discovered that eIF4E drives the production of certain proteins involved in the cleavage of mRNAs, a vital step in mRNA maturation. It also discovered that eIF4E directly binds the protein CPSF3, the enzyme responsible for 3’-end cleavage of mRNAs. Molecular biology experiments then established that eIF4E does not just passively bind mRNAs during the maturation steps of mRNAs in the nucleus, it actively participates in the process.
Because eIF4E is an oncoprotein, understanding its mechanisms of action could accelerate the development of cancer therapies. The IRIC team’s discovery adds an important layer of information to the role of this protein.
By Martin Primeau
Nuclear eIF4E stimulates 3’-end cleavage of target RNAs. Cell Reports.
M R Davis, M Delaleau, KLB Borden