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Biochim Biophys Acta. 2014 Jun;1839(6):452-62. doi: 10.1016/j.bbagrm.2014.04.007. Epub 2014 Apr 15.

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

Author information

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. Electronic address: elab@biogeo.uw.edu.pl.
3
Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Zwirki & Wigury 93, 02-089 Warsaw, Poland. Electronic address: wypijewska.del.nogal@gmail.com.

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 (m(7)GpppN), guarantee its resistance to non-specific exonucleases. DcpS enzymes are dimers belonging to the Histidine Triad (HIT) superfamily of pyrophosphatases. The specific hydrolysis of m(7)GpppN by DcpS yields m(7)GMP and NDP. By precluding inhibition of other cap-binding proteins by short m(7)GpppN-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:

HIT motif; cap; decapping scavenger enzyme; mRNA degradation; mRNA metabolism; spinal muscular atrophy

PMID:
24742626
DOI:
10.1016/j.bbagrm.2014.04.007
[Indexed for MEDLINE]

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