Decapping Scavenger (DcpS) enzyme: Advances in its structure,activity and roles in the cap-dependent mRNA metabolism |
| |
Authors: | Adina L Milac Elzbieta Bojarska Anna Wypijewska del Nogal |
| |
Institution: | 1. Department of Bioinformatics and Structural Biochemistry, Institute of Biochemistry of the Romanian Academy (IBAR), Splaiul Independentei 296, 060031, Bucharest 17, Romania;2. Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Zwirki & Wigury 93, 02-089 Warsaw, Poland |
| |
Abstract: | 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. |
| |
Keywords: | Aptx APraTaXin ARCA Anti-Reverse Cap Analog A suum Ascaris suum CBC Cap-Binding Complex C elegans Caenorhabditis elegans Dcp2 Decapping protein 2 DcpS Decapping Scavenger eIF4E eukaryotic translation Initiation Factor 4E Fhit Fragile HIstidine Triad Fre1 C elegans Flavin Reductase 1 GalT GALactose-1-P uridylylTransferase Hint HIstidine triad NucleoTide-binding HIT Histidine Triad m7GDP 7-methylguanosine diphosphate m7GMP 7-methylguanosine monophosphate m7GTP 7-methylguanosine triphosphate m7Guo 7-methylguanosine miRNA microRNA NES Nuclear Export Sequence NLS Nuclear Localization Signal NR1 human Novel Reductase 1 Nth1 neutral trehalase 1 PDB Protein Data Bank Por1 mitochondrial porin 1 RNAi RNA interference S cerevisiae Saccharomyces cerevisiae SMA Spinal Muscular Atrophy SMN Survival Motor Neuron VMD Visual Molecular Dynamics |
本文献已被 ScienceDirect 等数据库收录! |
|