Genome complexity: another layer of control is found (Introduction)

by David Turell , Friday, January 13, 2017, 01:15 (2659 days ago) @ David Turell

If the mRNA has one methyl or two methyls determines how much protein is produced:

http://www.news.cornell.edu/stories/2016/12/research-reveals-codes-control-protein-expr...

"In their study, published Dec. 21 in Nature, Jaffrey and lead author Jan Mauer, a postdoctoral associate in pharmacology at Weill Cornell Medicine, found that chemical marks called methyl groups are responsible for influencing individual mRNA’s stability. At the beginning of all mRNAs are so-called cap structures, previously thought only to dock cellular machines called ribosomes that string together amino acids to form proteins.

"The researchers have discovered that additional methyl marks are present on those caps, and that the position and number of methyl marks encode information that determines how stable mRNAs will be, and in turn, how much protein they will produce. mRNA caps containing two methyl groups cause the mRNA to be highly stable and lead to increased protein production, while mRNA caps with only one methyl group cause normal mRNA stability and result in lower protein levels.

"The investigators discovered the methyl mark encoding process by examining adenine, one of the genetic building blocks of mRNA. Scientists have long known that a single methyl can attach to adenosine, creating N6-methyladenosine (m6A). However, if present at the cap, adenosine can also have two methyl marks, creating m6Am.

***

"Many of these mRNAs contained instructions for making proteins that support cellular metabolism, survival and growth, and these proteins are typically essential for cellular proliferation.

"The investigators also found that the methyl marks can be added or removed, allowing an mRNA to switch from a highly stable state to a less stable state. They identified an enzyme – a fat mass and obesity-associated protein, or FTO – that can remove the methyl marks of m6Am, helping to restore normal mRNA stability and translation.

"Additionally, researchers were able to control cellular levels of m6Am by increasing or decreasing FTO. “If you don’t have the right levels of m6Am, gene expression may go haywire and you get disease,” Jaffrey said.

Comments from uncommon descent ID folks:

http://www.evolutionnews.org/2017/01/cornell_researc103412.html

"Another player is involved in this coding scheme. It's called FTO ("fat mass and obesity associated protein"). This enzyme can remove methyl groups from the cap adenosines, but it mostly goes after the doubly methylated m6am forms. Because of this, FTO regulates the stability of mRNAs. The Cornell team found that FTO was 100 times more likely to remove a methyl tag from m6am than from m6a.

"And then there's another player: DCP2. This enzyme "decaps" mRNAs, facilitating their degradation. Once decapped, mRNAs are degraded by micro-RNAs. The m6am RNAs, however, are more resistant to decapping by DCP2. This new epigenetic code helps explain why some mRNAs are more robust against degradation than others.

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"In their own words, the researchers consider this a coding system. "An internal code in cellular molecules called messenger RNA predetermines how much protein they will produce," Lindsey says. In the paper, the authors explicitly use the words code and information. In the Introduction, they say this:

"An emerging concept in gene expression regulation is that a diverse set of modified nucleotides is found internally within mRNA, and these modifications constitute an epitranscriptomic code.

And they repeat the concept in the concluding Discussion:

"Here we identify m6Am as a dynamic and reversible epitranscriptomic mark. In contrast to the concept that epitranscriptomic modifications are found internally in mRNA, we find that the 5′ cap harbours epitranscriptomic information that determines the fate of mRNA. The presence of m6Am in the extended cap confers increased mRNA stability, while Am is associated with baseline stability. m6Am has long been known to be a pervasive modification in a large fraction of mRNA caps in the transcriptome, making it the second most prevalent modified nucleotide in cellular mRNA. Dynamic control of m6Am can therefore influence a large portion of the transcriptome.

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"the location of the modified nucleotide and the specific combination of methyl groups on adenosine residues encode distinct functional consequences on the mRNA.

"The essence of a "code" is that it bears information. This code resembles an "if-then" algorithm in software. Speaking mechanistically, there's nothing about a methyl group that should indicate, "keep this attached molecule stable against degradation." Instead, the coding system works because all the players recognize the convention.

"The methyltransferase enzyme has to "know" which mRNA needs a second methyl group to confer stability, because it has an essential role. The FTO enzyme "knows" to concentrate on demethylating one tag from the m6am forms, and to stay inside the nucleus unless stimulated to go after m6am RNAs in the cytoplasm. And DCP2 has to know to avoid uncapping the doubly-methylated m6am transcripts. Because the players know the signal, the cell produces the appropriate quantity of proteins corresponding to their importance."

Comment: Code carries information. The various molecules 'know' because they are guided by information. Too complex for chance. How much complexity before God is required?