The human tRNA ligase complex 3 0 -5 0 RNA ligation appears to be the prevalent human tRNA splicing pathway [53, 56] and relies on HSPC117 as the essential ligase component as supported by two experimental observations: RNAi-mediated depletion of HSPC117 severely impairs tRNA maturation and mutation of a strictly conserved cysteine residue abolishes ligase activity of the affinity purified protein [103] . Human HSPC117, together with the proteins DDX1, CGI-99, FAM98B, and ASW, forms a stable complex of about 200 kDa (Fig. 4) [103] . Even earlier, the observed co-selection of HSPC117, DDX1, and CGI-99 with cruciform DNA duplexes hinted that these three proteins might interact [109] . In contrast to depletion of HSPC117, RNAimediated silencing of the associated proteins does not severely affect RNA ligase activity in HeLa cell extracts, suggesting further functions of the interacting proteins that remain to be explored [103] . Potential roles of these accessory proteins may include targeting of the complex to appropriate cellular compartments, stabilization of the essential subunit, interaction with substrates or adaptor proteins and prevention of illegitimate, promiscuous ligation. Moreover, individual complex components may mediate a transient association of the ligase complex with the tRNA endonuclease, as it has been suggested for the yeast tRNA endonuclease and ligase [110] . In contrast to its archaeal and bacterial orthologues, recombinant HSPC117 did not act as an RNA ligase in vitro. In addition, HSPC117 per se was incapable of replacing the yeast tRNA ligase TRL1 in complementation experiments (J. Popow, unpublished results).