Cap analog substrates reveal three clades of cap guanine-N2 methyltransferases with distinct methyl acceptor specificities.

RNA
Delphine BenarrochStewart Shuman

Abstract

The Tgs proteins are structurally homologous AdoMet-dependent eukaryal enzymes that methylate the N2 atom of 7-methyl guanosine nucleotides. They have an imputed role in the synthesis of the 2,2,7-trimethylguanosine (TMG) RNA cap. Here we exploit a collection of cap-like substrates to probe the repertoire of three exemplary Tgs enzymes, from mammalian, protozoan, and viral sources, respectively. We find that human Tgs (hTgs1) is a bona fide TMG synthase adept at two separable transmethylation steps: (1) conversion of m(7)G to m(2,7)G, and (2) conversion of m(2,7)G to m(2,2,7)G. hTgs1 is unable to methylate G or m(2)G, signifying that both steps require an m(7)G cap. hTgs1 utilizes a broad range of m(7)G nucleotides, including mono-, di-, tri-, and tetraphosphate derivatives as well as cap dinucleotides with triphosphate or tetraphosphate bridges. In contrast, Giardia lamblia Tgs (GlaTgs2) exemplifies a different clade of guanine-N2 methyltransferase that synthesizes only a dimethylguanosine (DMG) cap structure and cannot per se convert DMG to TMG under any conditions tested. Methylation of benzyl(7)G and ethyl(7)G nucleotides by hTgs1 and GlaTgs2 underscored the importance of guanine N7 alkylation in providing a key pi-cation i...Continue Reading

References

Jan 1, 1982·Annual Review of Biochemistry·H BuschY C Choi
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·G HuF A Quiocho
Aug 9, 2003·Nucleic Acids Research·John MouaikelRémy Bordonné
Dec 14, 2004·The Journal of Biological Chemistry·Stéphane Hausmann, Stewart Shuman
Jul 28, 2005·The Journal of Biological Chemistry·Stéphane Hausmann, Stewart Shuman
May 12, 2006·Molecular Biology of the Cell·Ira LemmReinhard Lührmann
Oct 5, 2007·Methods in Enzymology·Anna NiedzwieckaRyszard Stolarski
Oct 9, 2008·Journal of Cell Science·Jacqueline FrankeAnn E Ehrenhofer-Murray
Oct 30, 2008·Nucleic Acids Research·Augusto Simoes-BarbosaPatricia J Johnson
Feb 17, 2009·RNA·Delphine BenarrochStewart Shuman

❮ Previous
Next ❯

Citations

Aug 1, 2014·PloS One·Rehab F AbdelhamidPiero Carninci
Jan 31, 2012·Nucleic Acids Research·Jonathan ChangStewart Shuman
Jun 25, 2013·Angewandte Chemie·Daniela SchulzAndrea Rentmeister
Mar 11, 2015·Protein Engineering, Design & Selection : PEDS·Josephin Marie HolsteinAndrea Rentmeister
Nov 22, 2016·Chemistry : a European Journal·Josephin M HolsteinAndrea Rentmeister
Feb 16, 2019·Chembiochem : a European Journal of Chemical Biology·Nils MuthmannAndrea Rentmeister
Jul 19, 2018·Beilstein Journal of Organic Chemistry·Fabian MuttachAndrea Rentmeister

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.