Evolution took a long time: newly found epigenetics (Introduction)

by David Turell , Sunday, February 26, 2017, 20:27 (2827 days ago) @ David Turell

Research keeps unearthing how complex is the editing process that controls epigenetic modifications of gene function:

http://www.nature.com/news/an-epigenetics-gold-rush-new-controls-for-gene-expression-1....

"In 2012, two teams of researchers independently published the first maps of where m6A appears6, . The studies revealed more than 12,000 methylated sites on mRNAs originating from about 7,000 genes. “After years in the dark, we were instantly facing a wide vista,” wrote Dan Dominissini, an author of one of the studies, in an essay in Science.

"The maps showed that the distribution of m6A is not random. Its location suggested that the mark might have a role in alternative splicing of RNA transcripts, a mechanism that allows cells to produce multiple versions of a protein from a single gene.

***

"Over the past few years, researchers have identified some of the machinery involved in regulating these marks. Each requires a writer to place it, an eraser to remove it and a reader to interpret it. As the identities of these proteins emerged, scientists have come to understand that m6A affects not only RNA splicing, but also translation and RNA stability.

"One m6A reader, for example, makes mRNA degrade faster by shuttling it to decay sites in the cell. Another m6A reader promotes protein production by shepherding methylated RNA to the ribosome.

"Whether m6A directs a cell to produce a protein or destroy a transcript depends on the location of the mark and on the reader that binds to it. But understanding how this selection works has been a major challenge, says Gideon Rechavi, a geneticist at Tel Aviv University in Israel who was involved in the mapping of m6A.

"What is clear is that m6A has fundamental roles in cell differentiation. Cells that lack the mark get stuck in a stem- or progenitor-like state. That can be lethal: when He and his colleagues disabled the m6A writer in mice, many embryos died in utero.

"He has a possible explanation for the role of m6A. Each time a cell changes from one state to another — such as during differentiation — the mRNAs in it must change too. This change in mRNA content, which He calls a transcriptome switch, requires precision and careful timing. He thinks that the methyl marks might be a way for cells to synchronize the activity of thousands of transcripts.

***

"Xiao is still unravelling the function of 6mA. He says that it seems to be crucial at certain developmental stages, acting like a molecular switch — barely present one moment, then there's a surge, and then it disappears.

***

"There are still big questions to untangle. Mamta Tahiliani, a geneticist at New York University School of Medicine in New York City calls the 6mA work “incredibly exciting”, but points out that researchers haven't yet shown that the mark passes from one generation of cells to its progeny, a hallmark of epigenetic modifications.

"As some researchers dive deep to try to understand the function of m6A and 6mA, others are looking for new modifications. Last year, He, Rechavi and their colleagues reported. the discovery of another methyl mark on adenine in RNA called N1-methyladenosine (m1A). This mark also seems to promote translation, although the underlying mechanism is different from that of 6mA. He says it might also have a role in synchronizing transcripts for the transcriptome switch.

"Then, in January, Jaffrey and his colleagues reported on yet another kind of modification that occurs near the caps of mRNAs. The researchers found that mRNAs with this mark — called m6Am — are more stable because their caps are harder to remove. “It's exciting to people that the landscape of potentially regulated messenger RNA modifications that might influence gene expression could be an order of magnitude more complex than we thought before,” Gilbert says.

"Along with these new discoveries also come scientific squabbles. Jaffrey's work15 suggests that FTO, which He identified as an m6A eraser, actually targets m6Am. And in October, He's group reported16 that the enzyme Xiao flagged as a 6mA eraser on DNA actually does a better job of stripping m1A off a particular type of RNA. But such ambiguities are to be expected in a field that's experiencing a scientific gold rush."

Comment: Much of this research is involved in embryologic mechanisms, but it must also relate to simple adaptations. It doesn't look like a full blown IM creating major changes in species or evolving into new species. I've pared this giant article of most of the back history. It is worth reading.