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Structural highlights of the METTL3/METTL14 complex

[1]

This complex is composed of two differents proteins forming two distinct but linked subunit of the enzymatic complex/. Each of these two protein is coded by two differents genes. The mettl3 gene codes for the N6-adenosine-methyltransferase 70 kDa subunit, which is a 225 Amino acid chain, whereas the Mettl14 codes for the N6-adenosine-methyltransferase subunit METTL14, which is composed of 349 amino acids. Each of these two proteins are corresponding to the A [2]or the B chain [3] of the complex.

Thanks to their primary amino acid sequences both A and B chains have some specific conserved domains directly linked to their function and functionning.

Cristal structure

To study the crital structure of the METTL3/METTL14 some cristalograghy experiments have been realizes under the following experimental conditions :

Method : Vapor Diffusion Hanging Drop

pH 8

Temperature : 291.0 K

Buffer: 0.1 M Tris pH 8.0, 20% PEG3350

Thanks to the experiment the following data have been collected to describe the cristal structure of the complex :

Unit Cell caracteristics :

Length (Å) a = 101.86 b = 101.86 c = 117.66

Angle (°) α = 90 β = 90 γ = 90

Symmetry :

Space Group P 41 21 2

The primitive cubic symmetry of the unit cell is driven by X Z fold axis rotation. Moreover, within this space group which is acentric, chiral, and enantiomorphic with one single lattice translations, eight different representative symmetry operations are needed to get the whole unit cell.

Modification processes

Function of the modification within the cell

Specific, and well controlled methylation of the nucleic acids is essential for proper gene regulation, whatever the studied organism or modification’s type. However the precise molecular role of m6A is unknown, it is knonw that for most mRNAs, m6A modification appear in long exons, near stop codons, and in 3′ UTRs and that this modification could influence mRNA stability, induce RNA conformational changes, modulate protein-RNA interactions, and even modify microRNA processing One of the most prevalent modifications observed for mRNAs is N6-methyladenosine (m6A). Recent studies have intensely investigated how m6A-modification of RNA contributes to central events in biology. Nonfonctional m6A actors such as writers like METTL3 or METTL14, but also readers, and erasers are oftern linked to problems in self-renewal of stem cells, circadian clock and developmental defects, obesity, synaptic signaling, and cancers.

Disease and problems triggered by unfunctionnal METTL3/METTL14 complex

Relevance

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