A new way of epigenetic regulation of gene expression

A new epigenetic mRNA marker has been discovered

Oleg Lischuk, N+1

American and Israeli researchers have discovered a new pathway of methylation of matrix RNA (mRNA), which serves as an epigenetic marker regulating gene expression. The results of the work are published in the journal Nature (Dominissini et al., The dynamic N ¹-methyladenosine methylome in eukaryotic messenger RNA).

We are talking about an mRNA with adenosine methylated by a nitrogen atom in the first position (N1-methyladenosine, m1A). It is unusual in that at normal pH it has a positive charge (the other nitrogenous bases are not charged) and cannot form complementary bonds. The presence of m1A has been shown in transport RNA (tRNA), where it is necessary for the formation of the correct tertiary structure of the molecule. In mRNA and DNA, such methylation was observed under the action of alkylating agents and indicated damage to these nucleic acids. The study of m1A is difficult because in alkaline conditions it is converted by Dimrote rearrangement into the widespread epigenetic marker N6-methyladenosine (m6A).

Numbering of atoms in an adenine molecule (Pepemonbu / Wikimedia Commons)

Scientists from Chicago, Tel Aviv and Ramat Gan have developed a stabilization method that reduces the conversion rate in m6A to less than 10 percent. They also used radioactive labeling during mass spectrometry, which allowed them to conduct a quantitative analysis of m1A throughout the cell and find out its location in the mRNA molecule.

It turned out that, although m1A occurs many times less than m6A, it is present in thousands of transcripts. Moreover, in most mRNA molecules, it occurs only in sites rich in guanine and cytosine and associated with the thermodynamic stability of the secondary structure of the macromolecule. Further analysis showed that the proportion of mRNA containing m1A correlates with the level of gene expression. In addition, such mRNA is distinguished by a large number of sites initiating alternative translation. As a result, methylated mRNA produces 1.7 times more protein than unmethylated mRNA.

Experiments on cell cultures have shown that under various stressful conditions, the level of m1A can vary. That is, this nucleotide is a dynamic modification that plays a role in the response to stress and cellular signaling processes.

The data obtained suggest that m1A may be both a consequence of mRNA damage by alkylating agents and a useful epigenetic marker depending on its location in the molecule, Stanford chemists Anna Kietrys and Eric Kool, who did not participate in the study, note.

Epigenetic regulation of the phenotype does not affect the nucleotide sequences of genes, affecting only their expression. It can occur by methylation of nucleic acids, modification of histone proteins and some other ways.

Portal "Eternal youth" http://vechnayamolodost.ru 26.02.2015