How Elongator Acetylates tRNA Bases

Abstract

Elp3, the catalytic subunit of the eukaryotic Elongator complex, is a lysine acetyltransferase that acetylates the C5 position of wobble-base uridines (U34) in transfer RNAs (tRNAs). This Elongator-dependent RNA acetylation of anticodon bases affects the ribosomal translation elongation rates and directly links acetyl-CoA metabolism to both protein synthesis rates and the proteome integrity. Of note, several human diseases, including various cancers and neurodegenerative disorders, correlate with the dysregulation of Elongator’s tRNA modification activity. In this review, we focus on recent findings regarding the structure of Elp3 and the role of acetyl-CoA during its unique modification reaction.

Division of labor in epitranscriptomics: What have we learnt from the structures of eukaryotic and viral multimeric RNA methyltransferases?

“…The molecular strategies discussed in this review illustrate the division of labor between activating and catalytic subunits in RNA MTases. Some of these properties probably apply to other holoenzymes such as the Dcp1-Dcp2 mRNA decapping enzyme (Charenton & Graille, 2018), the Tad2-Tad3 A34-to-I34 tRNA deaminase (Gerber & Keller, 1999), the KEOPS and elongator complexes responsible respectively for the t 6 A37 and cm 5 U34 tRNA modifications (Abbassi, Biela, Glatt & Lin, 2020;Krutyholowa, Zakrzewski & Glatt, 2019;Thiaville, Iwata-Reuyl & de Crecy-Lagard, 2014), the human THUMPD1-NAT10 (Tan1-Kre33 in yeast) ac 4 C12 tRNA acetyltransferase (Sharma et al, 2015) or the Rtt109-Vps75 and Rtt109-Asf1 histone acetyltransferases (Kolonko et al, 2010;Lercher, Danilenko, Kirkpatrick & Carlomagno, 2018).…”

“Superwobbling” and tRNA-34 Wobble and tRNA-37 Anticodon Loop Modifications in Evolution and Devolution of the Genetic Code

“…The Elp3 enzyme class is as ancient as LUCA. These enzymes utilize S-adenosylmethionine, an iron-sulphur complex, acetyl coenzyme A and radical intermediates to methylate the 5-carbon of U34 [70][71][72]. The cm 5 U34 reaction appears to include multiple steps and cooperation of the S-adenosylmethionine and the lysine acetyltransferase homology (coenzyme A-binding) active sites.…”

“Superwobbling” and tRNA-34 wobble and tRNA-37 anticodon loop modifications in evolution and devolution of the genetic code

“…The Elp3 enzyme class is as ancient as LUCA. These enzymes utilize S-adenosylmethionine, an iron-sulphur complex, acetyl coenzyme A and radical intermediates to methylate the 5-carbon of U34 [69][70][71]. The cm 5 U34 reaction appears to include multiple steps and cooperation of the S-adenosylmethionine and the lysine acetyltransferase homology (coenzyme A-binding) active sites.…”