Decapping Scavenger (DcpS) enzyme: Advances in its structure, activity and roles in the cap-dependent mRNA metabolism

•Recent advances in the structure and activity of Decapping Scavenger (DcpS) enzyme;•Evaluation of DcpS roles in the cap-dependent mRNA metabolism;•Discussion of potential approaches to the SMA treatment based on DcpS inhibitors;•Overview of DcpS enzymes from different species: human, mouse, nematode and yeast.

Decapping Scavenger (DcpS) enzyme rids eukaryotic cells of short mRNA fragments containing the 5′ mRNA cap structure, which appear in the 3′ → 5′ mRNA decay pathway, following deadenylation and exosome-mediated turnover. The unique structural properties of the cap, which consists of 7-methylguanosine attached to the first transcribed nucleoside by a triphosphate chain (m7GpppN), guarantee its resistance to non-specific exonucleases. DcpS enzymes are dimers belonging to the Histidine Triad (HIT) superfamily of pyrophosphatases. The specific hydrolysis of m7GpppN by DcpS yields m7GMP and NDP. By precluding inhibition of other cap-binding proteins by short m7GpppN-containing mRNA fragments, DcpS plays an important role in the cap-dependent mRNA metabolism. Over the past decade, lots of new structural, biochemical and biophysical data on DcpS has accumulated. We attempt to integrate these results, referring to DcpS enzymes from different species. Such a synergistic characteristic of the DcpS structure and activity might be useful for better understanding of the DcpS catalytic mechanism, its regulatory role in gene expression, as well as for designing DcpS inhibitors of potential therapeutic application, e.g. in spinal muscular atrophy.