RNA editing and alternative splicing generate mRNA transcript diversity from the Drosophila 4f-rnp locus

Extensive sequencing of genomic 4f-rnp and 15 cDNA clones isolated from libraries of 0-4-h embryos, pupae, and adult heads from Drosophila melanogaster has enabled identification of factors resulting in transcript sequence diversity. The 4f-rnp gene contains eight small introns. Among non-edited cDNAs, one transcript class potentially encodes a 943-amino-acid protein, within which several motifs are predicted, including a single C-terminal RNA-binding domain. Intron 5 is retained in all cDNAs examined except for a pupal cDNA, where it is excised. This potentially introduces an in-frame stop codon and predicts a truncated protein of 639 amino acids. One adult head transcript class is edited, some 31% of As being converted to Gs exclusive of edits within introns. An edit site in intron 4 changes a canonical 3'-terminal AG to GG, which interferes with splicing and is predicted to introduce a stop codon. A potential editing substrate recognition element in 4f-rnp contains the weak consensus sequence: 5'-G-G-G-N-A-A-G-3', which may interact with double-stranded RNA adenosine deaminase following pairing of 4f-rnp mRNA with an antisense transcript. It is possible that extensive editing in 4f-rnp destabilizes transcripts and thus provides a novel mechanism for post-transcriptional control of gene expression, although resolution of this point will require study of additional edited transcripts.