- Date:
- June 14, 2017
- Source:
- Whitehead Institute for Biomedical Research
- Summary:
- The transition from an egg to a developing embryo is one of life’s most remarkable transformations. Now researchers have used fruit flies to decipher how one aspect — control of the translation of messenger RNAs (mRNAs) into proteins—shifts as the egg becomes an the embryo. This type of switch could tell scientists more about how human cells work and embryos develop.
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FULL STORY
The transition from an egg to a
developing embryo is one of life’s most remarkable transformations.
Whitehead Institute researchers have deciphered how one aspect—control
of the all-important translation of messenger RNAs (mRNAs) into
proteins—switches as the egg becomes an embryo. That shift is controlled
by a beautiful mechanism, which is triggered at a precise moment in
development and automatically shuts itself off after a narrow window of
20 to 90 minutes.
Credit: Image courtesy of Whitehead Institute for Biomedical Research
The transition from an egg to a
developing embryo is one of life's most remarkable transformations. Yet
little is known about it. Now Whitehead Institute researchers have
deciphered how one aspect -- control of the all-important translation of
messenger RNAs (mRNAs) into proteins -- switches as the egg becomes an
embryo. That shift is controlled by a beautiful mechanism, which is
triggered at a precise moment in development and automatically shuts
itself off after a narrow window of 20 to 90 minutes.
As an egg develops, it stockpiles mRNAs from the mother because it
will not have time to create new mRNAs during the rapid development of a
very early embryo. When fertilized the egg becomes an embryo, the
stashed maternal mRNAs are pressed into service for a brief window
before the embryo starts transcribing its own mRNAs. This change occurs
very early; in humans, only two to four cell divisions occur before this
transition is executed. Whitehead Member Terry Orr-Weaver studies the
control of translation of maternal mRNAs in the model organism Drosophila, or the fruit fly, because its developmental strategy offers experimental advantages.
In the current research, Orr-Weaver and her lab determined that key to the transition are the three molecules that form the enzyme PNG kinase: PNG, PLU, and GNU. Orr-Weaver describes PNG and PLU as "tight buddies" that are always locked together, including in the mature egg. At that point in development, GNU has phosphate molecules tacked to it, which impede its binding to PNG-PLU.
When an egg is activated, levels of another enzyme that adds phosphates to GNU in the egg precipitously drop, allowing GNU to lose its phosphates and bind to PNG-PLU. Once together, the trio comprises the PNG kinase that triggers the translational control of the maternal mRNAs. Because PNG kinase also triggers the break down of GNU, the kinase self-destructs, which quickly and irreversibly squelches the translation of maternal mRNAs. This elegant feedback loop and the switch it controls are described in an article in eLife.
The design of this transition could tell scientists more about how human cells work and embryos develop. For example, the switch could be a model for how cells massively and globally change mRNA translation. Also, similar kinase activity during early development has been noted in worms, which may mean that a comparable approach is used in other organisms, including humans.
Although she now has as greater understanding of how translation is turned on and off during very early embryonic development, Orr-Weaver is intrigued by how the switch is linked to the translation machinery.
"PNG is a kinase, which means it controls things by what it phosphorylates," says Orr-Weaver, who is also an American Cancer Society Research Professor of biology at MIT. "So the big question is what proteins does it phosphorylate? Finding that out is the next big phase of this project."
In the current research, Orr-Weaver and her lab determined that key to the transition are the three molecules that form the enzyme PNG kinase: PNG, PLU, and GNU. Orr-Weaver describes PNG and PLU as "tight buddies" that are always locked together, including in the mature egg. At that point in development, GNU has phosphate molecules tacked to it, which impede its binding to PNG-PLU.
When an egg is activated, levels of another enzyme that adds phosphates to GNU in the egg precipitously drop, allowing GNU to lose its phosphates and bind to PNG-PLU. Once together, the trio comprises the PNG kinase that triggers the translational control of the maternal mRNAs. Because PNG kinase also triggers the break down of GNU, the kinase self-destructs, which quickly and irreversibly squelches the translation of maternal mRNAs. This elegant feedback loop and the switch it controls are described in an article in eLife.
The design of this transition could tell scientists more about how human cells work and embryos develop. For example, the switch could be a model for how cells massively and globally change mRNA translation. Also, similar kinase activity during early development has been noted in worms, which may mean that a comparable approach is used in other organisms, including humans.
Although she now has as greater understanding of how translation is turned on and off during very early embryonic development, Orr-Weaver is intrigued by how the switch is linked to the translation machinery.
"PNG is a kinase, which means it controls things by what it phosphorylates," says Orr-Weaver, who is also an American Cancer Society Research Professor of biology at MIT. "So the big question is what proteins does it phosphorylate? Finding that out is the next big phase of this project."
Story Source:
Materials provided by Whitehead Institute for Biomedical Research. Original written by Nicole Giese Rura.
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