GLD-2

GLD-2, as a poly(A) polymerase (PAP) acts incorporating ATP at the 3' end of mRNAs in a template-independent manner.

It has been discovered that this protein has a catalytic activity, in other words, it has the ability to increase the speed of chemical reactions which would not occur so fast. It is known to catalysis the following reaction (which requires the following cofactor: Mg(2+)):

                            ATP + RNA(n)  ⇄  diphosphate  +  RNA(n+1)

Depending on the surroundings the optimal pH varies from 8 in the cytoplasm to 8.3 in the nucleus.

The GLD-2 protein together with 136 proteins more, is involved in the molecular process of hematopoietic progenitor cell differentiation, in the human proteome. This is the process in which precursor cell type acquires the specialized features of a hematopoietic progenitor cell, a kind of cell types including myeloid progenitor cells and lymphoid progenitor cells.

The polyadenylation activity of GLD-2, as we previously mentioned, is stimulated by physical interaction with an RNA binding protein, GLD-3. To test whether GLD-3 might stimulate GLD-2 by recruiting it to RNA, some studies tethered C. elegans GLD-2 to mRNAs in Xenopus oocytes by using MS2 coat protein. Tethered GLD-2 adds poly(A) and stimulates translation of the mRNA, demonstrating that recruitment is sufficient to stimulate polyadenylation activity. PAP heterodimer in which GLD-2 contains the active site and GLD-3 provides RNA-binding specificity. MS2 coat protein was joined to GLD-2 to recruit it to an RNA.

Furthermore, GLD-2 activity is also important to maintain or up-regulate the abundance of many mRNAs, as the cytoplasmic polyadenylation has an essential role in activating maternal mRNA translation during early development. In vertebrates, the reaction requires CPEB, an RNA-binding protein and the poly(A) polymerase GLD-2.

The Xenopus enzyme, which exists in two closely related forms, polyadenylates RNAs to which it is tethered and enhances their translation. Likewise, it interacts with cytoplasmic polyadenylation factors, including Cleavage and polyadenylation specificity factor and CPEB, and with target mRNAs. These findings confirm and extend a recent report that a GLD-2 enzyme is the long-sought PAP responsible for cytoplasmic polyadenylation in oocytes.

In addition, the formation of long-term memory is believed to lack translational control of localized mRNAs. In mammals, dendrite mRNAs are kept in a repressed state and are activated upon repetitive stimulation. Several regulatory proteins required for translational control in early development are thought to be needed for memory formation, suggesting similar molecular mechanisms. In an experiment using Drosophila, it has been detected the enzyme responsible for poly(A) elongation in the brain and it has been demonstrated too that its activity is required specifically for long-term memory. These findings provide strong evidence that cytoplasmic polyadenylation is critical for memory formation, and that GLD2 is the responsible enzyme.