Self‐Cleaving Ribozymes:

Twister
Twister‐Sister
Pistol
Hatchet

The Mg2+ ion (magnesium ion) is crucial for various biological functions, including those involving microtubules and ribozymes.

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Magnesium's vital role in mRNA ribozyme function

Magnesium ions (𝑀𝑔2+) are essential for the proper functioning of many ribozymes, including those that interact with or process messenger RNA (mRNA).

𝑀𝑔2+ plays a crucial role:

1. RNA folding and stabilization

𝑀𝑔2+ is generally required for the formation of the complex, three-dimensional (tertiary) structures that ribozymes need to become catalytically active.

These structures are stabilized by 𝑀𝑔2+ through interactions with the negatively charged phosphate groups in the RNA backbone. This effectively neutralizes repulsive forces that could prevent the RNA from folding correctly.In some ribozymes, such as the Tetrahymena group I intron, a core of 𝑀𝑔2+ ions is at the heart of the tertiary structure. These ions act as a scaffold around which the RNA folds.

Optimal 𝑀𝑔2+ concentrations are critical for the ribozyme to fold efficiently and avoid kinetic traps, where misfolded structures can form.

1. Catalysis

In addition to structural support, 𝑀𝑔2+ can directly participate in the catalytic mechanism of some ribozymes, assisting in the chemical reaction itself.For example, in the hammerhead ribozyme, 𝑀𝑔2+ ions stabilize the transition state during the cleavage reaction, potentially acting as a Lewis acid or by positioning critical residues for catalysis.

The exact mechanism of 𝑀𝑔2+'s catalytic role can vary between different ribozymes.

1. Specific examples and interactions

Hammerhead ribozyme:

Research suggests that 𝑀𝑔2+ plays a dual role in stabilizing the ribozyme's structure and directly participating in catalysis. QM/MM simulations indicate that 𝑀𝑔2+ binding in the active site helps form the proper conformation for cleavage and stabilizes the transition state.

GlmS ribozyme:

Research suggests that a 𝑀𝑔2+ near the cleavage site might be detrimental, while another 𝑀𝑔2+ position can be catalytically favorable by stabilizing negative charge and affecting the pKa of a key guanine base.

SAM/SAH riboswitch:

𝑀𝑔2+ ions are involved in the folding and conformational changes of this riboswitch, which binds S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH).

𝑀𝑔2+ can mediate ligand binding and conformational changes that affect gene expression.Tetrahymena ribozyme: Research has explored the optimal 𝑀𝑔2+ concentrations for the folding kinetics of this group I intron, highlighting the importance of balancing stable folding with avoiding kinetic traps.

In summary, magnesium ions are crucial cofactors for mRNA ribozymes, essential for their correct three-dimensional folding and often playing a direct role in the catalytic cleavage or modification of RNA molecules. The precise ways in which 𝑀𝑔2+ interacts with and influences ribozyme function are a key area of research in RNA biology.

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Magnesium & DNA

1. DNA Stability and Structure:

Magnesium ions bind to DNA, reducing the negative charge density and stabilizing the double helix structure.

This stabilization is crucial for maintaining genomic stability and proper DNA folding.

Increased magnesium concentration increases the melting temperature of DNA, making it more stable.

1. Enzyme Cofactor:

Magnesium is an essential cofactor for numerous enzymes involved in DNA processing & DNA polymerases.

Involved in DNA replication and require magnesium for primer extension and nucleotide incorporation.

DNA repair enzymes:

Such as those involved in nucleotide excision repair, base excision repair, and mismatch repair.

Other enzymes:

Magnesium is involved in various other DNA-related reactions, including DNA cleavage and ligation.

The two-metal-ion mechanism is a common way DNA polymerases utilize magnesium for catalysis.