Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm

We describe a novel RNA binding protein, Y14, a predominantly nuclear nucleocytoplasmic shuttling protein. Interestingly, Y14 associates preferentially with mRNAs produced by splicing but not with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Y14 associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Splicing of a single intron is sufficient for Y14 association. Y14-containing nuclear complexes are different from general hnRNP complexes. They contain hnRNP proteins and several unique proteins including the mRNA export factor TAP. Thus, Y14 defines novel intermediates in the pathway of gene expression, postsplicing nuclear preexport mRNPs, and newly exported cytoplasmic mRNPs, whose composition is established by splicing. These findings suggest that pre-mRNA splicing imprints mRNA with a unique set of proteins that persists in the cytoplasm and thereby communicates the history of the transcript.