This entry includes proteins with a radical SAM domain and a radical SAM C-terminal extension domain. One such protein is elongator complex protein 3 (ELP3): the catalytic histone acetyltransferase subunit of the RNA polymerase II elongator complex, which is itself part of the RNA polymerase II (RNAPII) holoenzyme responsible for transcriptional elongation []. A bacterial ELP3 homologue known as tRNA uridine(34) acetyltransferase, reflecting its role in mediating the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs is also included in this family []. This entry also includes protein YhcC from Escherichia coli , which binds an [4Fe-4S]cluster, coordinated with three cysteines and an exchangeable S-adenosyl-L-methionine. YhcC cleaves S-adenosyl-L-methionine into methionine and 5'-deoxyadenosine []. This entry also includes archaeosine synthase subunit beta (RaSEA) from archaea, it is a SAM enzyme which plays a role in the synthesis of archaeosine []. Uncharacterised homologues are known from bacteria, archaea and eukaryotes.ELP3 is required for the complex integrity and for the association of the complex with nascent RNA transcript []. ELP3 is thought to act as a highly conserved histone acetyltransferase (HAT) capable of acetylating core histones in vitro, however, it is clearly a multi-domain protein. The HAT activity is thought to be present only in the C-terminal GNAT domain (histone acyltransferase domain) []. Studies suggest that both the histone acetyltransferase and radical S-adenosylmethionine domains are essential for function, although the exact role of the Radical SAM domain is still unclear []. The radical SAM domain is important for the structural integrity of the protein complex, as in yeast (previously demonstrated) []. However, an alternative may be that ELP3 binds ands cleave SAM, as seen in the archaea M. jannaschii. It has also been shown in previous studies that the mouse ELP3 does not require the histone acyltransferase domain for zygotic paternal genome demethylation [].
The elongator complex is a major component of the RNA polymerase II (RNAPII) holoenzyme responsible for transcriptional elongation. It binds to both naked and nucleosomal DNA, can acetylate both core and nucleosomal histones, and is involved in chromatin remodelling []. It acetylates histones H3, preferentially at 'Lys-14', and H4, preferentially at 'Lys-8'. ELP3 is required for the complex integrity and for the association of the complex with nascent RNA transcript. ELP3 is thought to act as a highly conserved histone acetyltransferase (HAT) capable of acetylating core histones in vitro, however, it is clearly a multi-domain protein. The HAT activity is thought to be present only in the C-terminal GNAT domain (histone acyltransferase domain). Recent work []suggests that both the histone acetyltransferase and radical S-adenosylmethionine domains are essential for function, although the exact role of the Radical SAM domain is still unclear. The radical SAM domain is important for the structural integrity of the protein complex, and in yeast (previously demonstrated) []. However, an alternative may be that ELP3 binds and cleave SAM, as seen in the archaean M. jannaschii. It has also been shown in previous studies that the mouse ELP3 does not require the histone acyltransferase domain for zygotic paternal genome demethylation [, , , ].The archaeal protein which is the homologue of the third subunit of the eukaryotic elongator complex (Elp3), catalyses the tRNA wobble uridine modification at C5: the same reaction as the eukaryotic elongator complex. The proposed mechanism of action by Elp3 represents an unprecedented chemistry performed on acetyl-CoA in which the methyl group of the acetly-CoA is activated by the 5'-deoxyadenosyl radical. This then adds to the uridine of tRNA []. Some bacterial ELP3 homologues are known as tRNA uridine(34) acetyltransferase [].
