Identification of the yeast cytidine deaminase CDD1 as an orphan C -> U RNA editase

Yeast co-expressing rat APOBEC-1 and a fragment of human apolipoprotein B ( apoB) mRNA assembled functional editosomes and deaminated C6666 to U in a m ooring sequence-dependent fashion. The occurrence of APOBEC-1-complementing proteins suggested a naturally occurring mRNA editing mechanism in yeast. Previously, a hidden Markov model identified seven yeast genes encoding pro teins possessing putative zinc-dependent deaminase motifs, Here, only CDD1, a cytidine deaminase, is shown to have the capacity to carry out C -->U ed iting on a reporter mRNA, This is only the second report of a cytidine deam inase that can use mRNA as a substrate. CDD1-dependent editing was growth p hase regulated and demonstrated mooring sequence-dependent editing activity . Candidate yeast mRNA substrates were identified based on their homology w ith the mooring sequence-containing tripartite motif at the editing site of apoB mRNA and their ability to be edited by ectopically expressed APOBEC-1 , Naturally occurring yeast mRNAs edited to a significant extent by CDD1 we re. however, not detected. We propose that CDD1 be designated an orphan C - ->U editase until its native RNA substrate, if any, can be identified and t hat it be added to the CDAR (cytidine deaminase acting on RNA) family of ed iting enzymes.