Genome complexity: new epigenetic discoveries (Introduction)

by David Turell , Friday, February 14, 2025, 19:20 (22 days ago) @ David Turell

DNA and RNA work together to control gene expression:

https://www.livescience.com/health/genetics/scientists-just-rewrote-our-understanding-o...

"Now, in a study published Jan. 17 in the journal Cell, scientists have uncovered a whole new method of gene regulation that involves epigenetic tweaks made to both DNA and its molecular cousin RNA, at the same time.

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"In recent years, researchers have also found that RNA — a molecule that shuttles instructions from DNA out into the cell to make proteins — can also be modified. This is mainly done by a protein complex called METTL3-METTL14. This methylation can destabilize the RNA molecule, reducing the amount of protein made.

"Every cell in the body uses both RNA and DNA methylation to regulate gene expression. However, it was previously assumed that these processes operated independently. The new study puts that assumption into question.

"In the study, the scientists looked at mouse embryonic stem cells and mapped the locations of DNA and RNA methylation as the cells developed. They found that thousands of genes and their complementary RNA molecules contained both methylation markers.

"Through additional experiments, the team found that the METTL3-METTL14 complex that interacts with RNA also recruits and physically binds to DNMT1, the protein that tags DNA. This new, bigger complex can then methylate the same gene at the DNA or RNA level. This enables the cell to further fine-tune its gene regulation during cell differentiation — a process by which a stem cell assumes a specific identity, becoming a heart or lung cell, for example.

"Previous studies have shown clear connections between DNA and histone modifications, as well as between histone and RNA modifications.

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"[Our study shows] the direct connection between DNA methylation and RNA modification that has not been seen before," he told Live Science.

"According to Fuks, this study does have some limitations, namely, that it mostly focuses on embryonic stem cell differentiation. DNA and RNA modifications had separately been well characterized in stem cells in past studies, so it made sense for the researchers to start with them. But these same types of DNA and RNA modifications are present in all types of cells.

"'Seeing this, it's very unlikely that [this mechanism] will be just in ES cells," Fuks said.

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"If the coordination of DNA and RNA epigenetics gets thrown off, you may end up with too much or too little of a protein, Fuk suggested. "Now, a key protein will be expressed at a too high level," he said."This could be detrimental for a cell and contribute to tumorigenesis," or the formation of tumors."

Comment: this is a logical discovery from a design standpoint. DNA and RNA need to work hand- in-hand to fine-tune protein production levels to exact amounts.