Metal ghosts in the splicing machine

摘要

Genes are transcribed as pre-messenger RNA molecules in which the coding exon segments are typically interrupted with non-coding sequences, or introns. To create a functional mRNA, the introns must be removed and the exons joined together in a process known as pre-mRNA splicing. The two phosphoryl-transfer reactions of splicing are catalysed by the spliceosome, a metallo-enzyme complex comprising five small nuclear RNAs (snRNAs) and dozens of core proteins1. The spliceosome uses magnesium ions at its active site as catalytic cofactors, and researchers have long been captivated by the question of whether the ligands for these metal ions are provided by the snRNAs or by the proteins, as this speaks to the evolutionary roots of the splicing process. On page 229 of this issue, Fica et al~2 report that a specific constellation of phosphate oxygens in the U6 snRNA supplies the ligands that coordinate the catalytic metal cofactors in the active site. This finding establishes the concept that pre-mRNA splicing is fundamentally an RNA-catalysed reaction.