Splicing factor SF1 from Drosophila and Caenorhabditis: Presence of an N-terminal RS domain and requirement for viability

Splicing factor SF1 contributes to the recognition of the 3' splice site by interacting with U2AF(65) and binding to the intron branch site during the formation of the early splicing complex E. These interactions and the esse ntial functional domains of SF1 are highly conserved in Saccharomyces cerev isiae. We have isolated cDNAs encoding SF1 from Drosophila (Dm) and Caenorh abditis(Ce). The encoded proteins share the U2AF(65) interaction domain, a hnRNP K homology domain, and one or two zinc knuckles required for RNA bind ing as well as Pro-rich C-terminal sequences with their yeast and mammalian counterparts, In contrast to SF1 in other species, DmSF1 and CeSF1 are cha racterized by an N-terminal region enriched in Ser, Arg, Lys, and Asp resid ues with homology to the RS domains of several splicing proteins. These dom ains mediate protein-protein or protein-RNA interactions, suggesting an add itional role for DmSF1 and CeSF1 in pre-mRNA splicing, Human (Hs), fly, and worm SF1 interact equally well with HsU2AF(65) or the Drosophila homolog D mU2AF(50). Moreover, DmSF1 lacking its N terminus is functional in presplic eosome formation in a HeLa splicing system, emphasizing the conserved natur e of interactions at an early step in spliceosome assembly, The Ce-SF1 gene is located in a polycistronic transcription unit downstream of the genes e ncoding U2AF(35) (uaf-2) and a cyclophilin (cyp-13), implying the coordinat e transcriptional regulation of these genes, Injection of double-stranded R NA into C. elegans results in embryonic lethality; thus, the SF1 gene is es sential not only in yeast but also in at least one metazoan.