November 27, 2023
Hokkaido University
Keio University School of Medicine
A research group led by Associate Professor Tomoya Kotani of the Faculty of Science, Hokkaido University, in collaboration with Senior Lecturer Takehiro Yamamoto of the Department of Biochemistry, Keio University School of Medicine, has discovered that mature mRNA becomes shorter, thereby elucidating a new mechanism for animal birth.
mRNA transcribed in the cell nucleus has its length and sequence determined before being transported to the cytoplasm, becoming mature mRNA. It was previously thought that the length of mature mRNA does not change. Furthermore, while animal zygotes synthesize proteins from mRNA to advance development, it is believed that the location and timing of this synthesis must be strictly controlled. The research group discovered that mRNA stored in animal zygotes is partially shortened at a certain stage of development. Specifically, they found that the 3' end sequences of zebrafish *pou5f3* mRNA and mouse *Pou5f1* mRNA are shortened by approximately 70 and 10 bases, respectively. Next, they demonstrated that the long mRNA is translationally repressed and does not synthesize protein, whereas the shortened mRNA activates translation and synthesizes protein. Furthermore, they revealed that in embryos where mRNA shortening was inhibited, translation was not activated, and these embryos subsequently developed with extremely short head-to-tail axes and ceased development. Through comprehensive analysis and functional analysis using antibodies, it was shown that mRNA shortening acts as a molecular switch that swaps binding proteins. Finally, they analyzed length changes in 568 types of mRNA, corresponding to about 5% of the mRNA in a zygote, and showed that shortening occurs in over 40% of these mRNAs. This research has successfully uncovered a critically important principle for how zygotes advance development.
These research findings were published in the journal *Science Advances* on Friday, November 24, 2023.
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