[Sis290025]

Does cyclic AMP occur naturally in messenger RNA?

Thanks.

[Yggdrasil]

No.  cyclic-AMP (cAMP) is produced in the cytoplasm by the enzyme adenylyl cyclase.  Recall that nucleotides are incorporated into nucleic acids by linking the 5' hydroxyl to the 3' hydroxyl of a neighboring nucleotide via a phosphodiesterase bond.  Therefore, in order to be incorporated into a nucleic acid, the 5' or 3' hydroxyl must be free to form a bond.  However, in cAMP, the 5' and 3' hydroxyls are involved in an intramolecular phosphodiesterase bond, so cAMP cannot be incorporated into RNA.

Instead, cAMP primarily plays a role as a signaling molecule in the cell.  cAMP is synthesized by adenylyl cyclase at the plasma membrane when a transmembrane receptor (specifically a G-protein coupled receptor [GPCR]) is activated.  cAMP then diffused away from the membrane and activates an enzyme called protein kinase A (PKA).  Activation of PKA by cAMP allows PKA to enter the nucleus and activate various transciption factors.  Therefore, cAMP plays an essential role in shuttling a signal from the outside of the cell (ligand binding to receptor) into the nucleus of the cell where the signal can turn on the expression of specific genes.

[Sis290025]

cAMP (adenosine 3',5'-cyclic monophosphate) is different from adenosine 2',3'-cyclic monophosphate, right? It does not have an intramolecular bond like in cAMP, so can it occur naturally in a nucleic acid, such as RNA?

Thanks again.

[Yggdrasil]

Possibly.  Adenosine 2',3'-cyclic monophosphate still does have an intramolecular phosphodiester bond, but this time the bond bridges the 2' and 3' hydroxyls, leaving a free 5' hydroxyl.  Therefore, if the 5' OH were to have three phosphates placed onto it, it could theoretically be incorporated at the 3' end of a nucleic acid.  The nucleic acid, however, could not continue beyond this point without breaking the cyclic phosphodiester bond in order to free up the 3' hydroxyl of the adenosine 2',3'-cyclic monophosphate.

Although this could happen in principle, this doesn't mean that this phenomenon actually occurs in natural mRNAs.  Various factors (such as whether cells can make this compound and whether this nucleotide can fit into RNA polymerase's active site) could prevent the natural incorporation of this molecule into mRNA.

[Sis290025]

Does inosine monophosphate (inosine 5'-monophosphate)
 exist in a nucleic acid? If so, which nucleic acid does it occur in?


Thanks again.

[Yggdrasil]

Inosine monophosphate, and many other non-standard bases, are commonly found in tRNAs.