The eukaryal tRNA endonucleases are phylogenetically related to their archaeal counterparts [39] . The yeast endonuclease is of the abcd type and consists of two catalytic subunits, ScSEN2 and ScSEN34, and two structural subunits, ScSEN15 and ScSEN54 [37]. All four yeast subunits have homologous human proteins termed HsTSEN2, HsTSEN34, HsTSEN15, and HsTSEN54 [38] . Although it has been shown that at least one eukaryal tRNA endonuclease retained the ability to process archaeal pre-tRNA substrates [46] , eukaryal endonucleases seem to have a different mode of splice site recognition: Eukaryal tRNA endonucleases cleave pre-tRNA substrates at a conserved distance from a structural feature located in the mature domain [47] . Apart from a strictly conserved A:I base pair (Fig. 1B ) [48] , little sequence constraint seems to exist for the intron itself, which can be extensively mutated without disturbing its proper recognition by the endonuclease [49] .