Virus-Like “Jumping” DNA Regulates Human Neurons

[shunyadragon]

Source: https://scitechdaily.com/virus-like-jumping-dna-regulates-human-neurons/

Virus-Like “Jumping” DNA Regulates Human Neurons

The human genome contains over 4.5 million sequences of DNA called “transposable elements,” these virus-like entities that “jump” around and help regulate gene expression. They do this by binding transcription factors, which are proteins that regulate the rate of transcription of DNA to RNA, influencing gene expression in a broad range of biological events.

Now, an international team of scientists led by Didier Trono at EPFL has discovered that transposable elements play a significant role in influencing the development of the human brain. The study is published in Science Advances.

The scientists found that transposable elements regulate the brain’s development by partnering up with two specialized proteins from the family of proteins known as “Krüppel-associated box-containing zinc finger proteins, or KZFPs. In 2019, another study led by Trono showed that KZFPs tamed the regulatory activity of transposable elements in the first few days of the fetus’s life. However, they suspected that these regulatory sequences were subsequently re-ignited to orchestrate the development and function of adult organs.

The researchers identified two KZFPs as specific only to primates, and found that they are expressed in specific regions of the human developing and adult brain. They further observed that these proteins kept controlling the activity of transposable elements — at least in neurons and brain organoids cultured in the lab. As a result, these two KZFPs influenced the differentiation and neurotransmission profile of neurons, as well as guarded these cells against inflammatory responses that were otherwise triggered if their target transposable elements were left to be expressed.

“These results reveal how two proteins that appeared only recently in evolution have contributed to shape the human brain by facilitating the co-option of transposable elements, these virus-like entities that have been remodeling our ancestral genome since the dawn of times,” says Didier Trono. “Our findings also suggest possible pathogenic mechanisms for diseases such as amyotrophic lateral sclerosis or other neurodegenerative or neurodevelopmental disorders, providing leads for the prevention or treatment of these problems.”

Reference: “Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons” by Priscilla Turelli, Christopher Playfoot, Dephine Grun, Charlčne Raclot, Julien Pontis, Alexandre Coudray, Christian Thorball, Julien Duc, Eugenia V. Pankevich, Bart Deplancke, Volker Busskamp and Didier Trono, 28 August 2020, Science Advances.
DOI: 10.1126/sciadv.aba3200.

© Copyright Original Source

[shunyadragon]

The importance of this discovery was not that the fact that it was discovered in humans with unique human proteins, but that it was a virus like 'Gene Jumping' that regulates Human neurons. Virus like behavior mechanism here has a unique place in the close relation with viruses in nature of evolution

[TheLurch]

That paper is not as interesting as the press release suggests. The background for the study is that:
There are transposable elements scattered throughout nearly every animal genome.
Primates have evolved proteins that bind to sequences within them and shut down the activity of the genes in the transposable element.
If this shut down fails, the transposable element genes become active, and proteins are made.
The immune system reacts to these proteins and can kill the cells in which they're active.

What's new here is that the authors show that the proteins that shut down the transposable element activity don't have that process limited to the transposon itself - if there are nearby genes, they get partly shut down as well. This isn't a huge surprise, but it's something that, over time, evolution has found a use for, as it seems to be involved in shutting down non-neural genes more often than you'd expect at random.