Drosophila clipper/CPSF 30K is a post-transcriptionally regulated nuclear protein that binds RNA containing GC clusters

An essential component of the mammalian pre-mRNA. 3'-end processing machinery isa multimeric protein complex known as cleavage and polyadenylation specificity factor (CPSF), The Drosophila melanogaster gene, clipper (clp), encodes a homolog of the CPSF 30K subunit, We have shown previously that CLP possesses N-terminal endoribonucleolytic activity and that the relative expression of its mRNA fluctuates during fly development. In the present study, we report that CLP's C-terminus, containing two CCHC zinc knuckles, confers a binding preference for RNAs that contain G- and/or C-rich clusters. We also show, for the first time, that a member of the highly conserved CPSF 30K family is a nuclear and developmentally regulated protein. Though clp transcripts are detectable throughout embryogenesis, CLP protein is not present. We demonstrate that post-transcriptional regulation of clp mRNA in the embryo occurs by a process that does not involve poly(A) tail length shortening. Thus, a key component of the pre-mRNA 3'-end processing machinery is subject to post-transcriptional regulation during development. These results support the existence of a distinct mechanism controlling eukaryotic gene expression through the regulated processing of pre-mRNAs in the nucleus.