Gene Description Localization Gene Family Function N-acetylglucosamine-1-phosphodiester Nucleus; Cytoplasm alpha-N-acetylglucosaminidase SERPINE1 mRNA binding protein 1 cyclin-dependent kinase 4 CDC14 cell division cycle 14 homolog A (S. cerevisiae) BCL6 co-repressor ribosomal protein L5 nucleolar protein 1, 120kDa pyruvate kinase, muscle ethanolamine kinase 1 Nucleus Nucleus Nucleus Cytoplasm Cytoplasm Polysome Cytoplasm; Polysome Cytoplasm; Polysome mitogen-activated protein kinase 3 Cytoplasm eukaryotic translation elongation factor 1 alpha 1 Nucleus; Cytoplasm; Polysome enzyme other kinase other other kinase kinase kinase translation phosphatase dual specificity protein tyrosine phosphatase transcription regulator Transcriptional corepressor carbohydrate metabolic process; lysosome organization and biogenesis mRNA processing Cell Cycle Regulation Ribosome Component Cell Cycle Regulation; RNA Methyltransferase Glycolytic enzyme phosphatidylethanolamine biosynthetic process intracellular signaling cascade translational elongation doi:10.1371/journal.pone.0003369.t003 (Fig. 2 and Table S1). These data revealed a set of mRNAs whose splicing and translation may be coordinated by SF2/ASF. Collectively, our data do not support the view that SF2/ASF plays a general role in mRNA translation, but suggests that the biological importance of this aspect of SF2/ASF function may be at transcript and cell types-specific events. Our recent findings that mTOR is critical to translational control by SF2/ASF suggest that SF2/ASF may connect cellular signal transduction pathways with post-transcriptional control of specific target mRNAs [9]. Using the CLIP approach we were able to not only identify potential RNA targets for SF2/ASF but also define a consensus binding motif present in exonic binding sites (Fig. 3). This purine- rich motif closely resembles the well-characterized exonic splicing enhancers (ESE) present in the fibronectin EDA alternative cassette exon as well as exon 5 of the cardiac troponin T (cTNT) gene [30,31]. The binding specificity of SR proteins has also been extensively studied using SELEX strategies. Our data are in good agreement from results obtained using only the RRM domains of Table 4. Annotated as described in Table 1. SF2/ASF target exons containing a retained intron Gene Description ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide ATPase, Cu++ transporting, beta polypeptide Nucleus transporter eukaryotic translation elongation factor 1 alpha 1 Localization Gene Family Function Nucleus; Cytoplasm transporter Nucleus; Cytoplasm; translation regulator translational elongation Polysome Table 3. Annotated as described in Table 1. SF2/ASF target exons containing alternative 59 splice sites SF2/ASF RNA Targets Gene ID NAGPA SERBP1 CDK4 CDC14A BCOR RPL5 NOL1 PKM2 ETNK1 MAPK3 EEF1A1 Exon Position 5 6 2 4 1 2 2 6 15 16 2,3,6 Gene ID ATP5B ATP7B EEF1A1 GNL3 NAGPA RAN RPL12 RPL23 RPLP0 SFRS1 TH1L TSSC4 WDR59 ZMYM3 Exon Position 13 2 2 1 5 7 7 3 5 4 15 4 12 7 doi:10.1371/journal.pone.0003369.t004 PLoS ONE | www.plosone.org guanine nucleotide binding protein-like 3 (nucleolar) Cytoplasm N-acetylglucosamine-1-phosphodiester alpha-N- acetylglucosaminidase RAN, member RAS oncogene family Nucleus; Cytoplasm ribosomal protein L12 ribosomal protein L23 ribosomal protein, large, P0 splicing factor, arginine/serine-rich 1 (splicing factor 2, Cytoplasm alternate splicing factor) TH1-like (Drosophila) tumor suppressing subtransferable candidate 4 WD repeat domain 59 zinc finger, MYM-type 3 other enzyme enzyme other other other other other other other transporter Nucleus Nucleus Polysome Nucleus Cytoplasm Nucleus Nucleus Cytoplasm 6 generation of precursor metabolites and energy cellular copper ion homeostasis Stem Cell Proliferation carbohydrate metabolic process; lysosome organization and biogenesis GTP-binding protein involved in nucleocytoplasmic transport Ribosome Component Ribosome Component Ribosome Component mRNA processing Transcription regulator Unknown Not Determined multicellular organismal development October 2008 | Volume 3 | Issue 10 | e3369