A novel human gene denominated TruB
pseudouridine (psi) synthase homolog 1 (E. coli) (approved symbol, TRUB1) has been identified and characterized. Spanning approximately 40 kb on chromosome 10 and including 8 exons, TRUB1 is the first described human ortholog of bacterial TruB/psi55, a gene involved in
tRNA pseudouridinilation. TRUB1 gene encodes a 349-amino
acid product, with a VFAVHKPKGPTSA box in positions 71-83 corresponding to motif I of the TruB family (probably involved in conserving
protein structure). The TruB domain of TRUB1 lies between W104 and I255, and contains another short motif, GGTLDS AARGVLVV, including the highly conserved D residue that characterizes motif II (involved in
uridine recognition and in catalytic function of psi synthases). Northern blot analysis revealed that TRUB1
mRNA is widely expressed in various human tissues (especially heart, skeletal muscle and liver). Phylogenetic analysis of the TruB domain revealed another human gene (approved symbol TRUB2) encoding a conserved TruB domain, located on human chromosome 9. Thus, the human TruB family includes at least three members: i.e. DKC1 (previously identified), TRUB1 and TRUB2. The TRUB1 and TRUB2 products could be the hitherto unidentified human
tRNA psi synthases. Although TRUB1 is not highly similar to DKC1/dyskerin (whose mutations cause
X-linked dyskeratosis congenita) and putatively affects
tRNA rather than rRNA modification, it is the most similar human
protein to dyskerin. Study of TRUB1 (and TRUB2) should facilitate understanding of the molecular mechanisms of
RNA modification and the involvement of psi synthases in human pathology, including dyskeratosis-like diseases.