The human tRNA ligase complex components seem to be constitutively and widely expressed in all human and mouse tissues analyzed so far, indicating that these proteins cooperate in a great variety of cellular contexts [103, 111, 112] . DDX1 is a member of the DEAD-box family of putative RNA helicases characterized by the presence of nine conserved sequence motifs [113] . The DEAD-box helicase domain of DDX1 is interrupted by the insertion of a SPRY domain (Fig. 4 ) detectable in numerous proteins and presumably acting as a protein interaction platform [114, 115] . DDX1 has been associated with many molecular functions ranging from mRNA processing [116, 117] to recognition of DNA double-strand breaks [118] and has been demonstrated to exhibit 3 0 -5 0 RNA unwinding activity [117] . The association of DDX1 with HSPC117 suggests an involvement in tRNA splicing. On the other hand, RNAi-mediated depletion of DDX1 only mildly impaired tRNA maturation activity, suggesting that its function might be dispensable for RNA ligation by HSPC117 in HeLa cell extracts [103] . Alternatively, a lack of DDX1 might also have been compensated for by other proteins present in the assayed extracts. Further experiments assessing the effect of mutations within conserved motifs of DDX1 on ligase activity-carried out with purified RNA ligase complex-might successfully address the function of this protein in tRNA splicing. Co-localization studies and extended analysis of proteins associating with DDX1 could answer the question whether DDX1 mediates its functions in conjunction with HSPC117 or whether it is a shared component of multiple protein complexes acting in distinct biological processes. Furthermore, it might be rewarding to test whether the amplification of DDX1 observed in cancerous cell lines [111, 119, 120] , its function in viral replication [121] [122] [123] , and dsRNA recognition in dendritic cells [124] are linked to RNA ligase activity or tRNA processing. Published information concerning the function of CGI-99 is scarce. Although the protein has been found to interact with human [112, 125] and viral [125] proteins in yeast two-hybrid assays, these studies provided little insight into its molecular function. It remains to be determined whether the interaction of CGI-99 with the PA subunit of influenza virus polymerase [125] or its modulation of transcription by RNA polymerase II [126] is in any respect related to RNA ligase activity.