HGNC Approved Gene Symbol: RNPS1
Cytogenetic location: 16p13.3 Genomic coordinates (GRCh38) : 16:2,253,116-2,268,126 (from NCBI)
Splicing of mRNA must be highly precise to carry the correct genetic information to the cytoplasm as templates for translation. On the other hand, it is also flexible to allow for alternative splicing, which can permit tissue-specific and physiologically and developmentally controlled regulation of gene expression. The splicing process involves more than 50 proteins in the splicing complex, or spliceosome. RNPS1 regulates alternative splicing of a variety of pre-mRNAs.
By screening an osteosarcoma cDNA library with a probe encompassing the osteocalcin (112260) vitamin D response element, followed by probing a hippocampus cDNA library, Badolato et al. (1995) isolated a cDNA encoding RNPS1, which they termed E5.1. Sequence analysis predicted that the 305-amino acid RNPS1 protein has long stretches that are 100% identical to the mouse protein. RNPS1 has a long N-terminal ser-rich (SR) region; a 90-residue RNA recognition motif that contains RNP1 and RNP2 submotifs; an SR splicing protein motif; 2 arg-rich RNA-binding domains; and a C-terminal nuclear localization signal. Northern blot analysis revealed ubiquitous expression of a 2.4-kb RNPS1 transcript. There was no significant change in expression during cell cycle progression or after treatment with progestin.
By yeast 2-hybrid, coimmunoprecipitation, and Western blot analyses, Loyer et al. (1998) showed that the N terminus of the p110 isoform of PITSLRE (see CDC2L1; 176873), but not other isoforms, interacts with the N-terminal RNA-binding domain of RNPS1. Immunofluorescence analysis demonstrated the expression of both proteins in large nuclear speckles.
Mayeda et al. (1999) showed that expression of RNPS1 synergizes with SR proteins to strongly activate splicing of constitutively and alternatively spliced pre-mRNAs.
By Northern blot analysis, Lykke-Andersen et al. (2001) determined that expression of RNPS1 or UPF3B (300298), and to a lesser extent Y14 (RBM8A; 605313), in the presence of wildtype or dominant-negative UPF1 (RENT1; 601430) marks the mRNA for nonsense-mediated decay (NMD) when tethered to the 3-prime untranslated region of beta-globin mRNA. This did not occur with DEK (125264), ALY (604171), or SRM160 (605975). Fluorescence microscopy demonstrated that RNPS1 is a nucleocytoplasmic shuttling protein. Coimmunoprecipitation analysis indicated high levels of RNPS1 association with UPF3A (605530), UPF3B (2 splice variants each), UPF2 (605529), and UPF1. Y14 and TAP (NXF1; 602647) were also found in the complexes and all assembled at exon-exon junctions. Lykke-Andersen et al. (2001) concluded that the post-splicing proteins Y14, RNPS1, and UPF3B remain on the mRNA after binding to the mRNA export receptor NXF1, while ALY and SRM160 dissociate. If termination occurs upstream of the last exon-exon junction, mRNA decapping is triggered followed by rapid NMD.
By yeast 2-hybrid analysis with full-length RNPS1 and several deletion mutants, Sakashita et al. (2004) identified several splicing-related factors that interacted with the various domains of RNPS1 in HeLa cells. SFRS11 (600326), pinin (603154), and TRA2B (602719) interacted with the N-terminal serine-rich domain, the central RNA recognition motif (RRM), and the C-terminal arginine/serine/proline-rich (RSP) domain of RNPS1, respectively. Protein-protein binding between RNPS1 and these factors was verified in vitro and in vivo. Overexpression of RNPS1 in HeLa cells induced exon skipping in a model beta-globin pre-mRNA and human TRA2B pre-mRNA. Coexpression of RNPS1 and SFRS11 cooperatively stimulated exon inclusion in an ATP synthase gamma subunit (108729) pre-mRNA. The RSP domain and RRM were necessary for the exon-skipping activity, whereas the serine-rich domain was important for the cooperative effect with SFRS11. Sakashita et al. (2004) concluded that RNPS1 is a versatile factor that regulates alternative splicing of a variety of pre-mRNAs.
By exon trapping of a P1 contig, Burn et al. (1996) mapped the RNPS1 gene to 16p13.3.
Badolato, J., Gardiner, E., Morrison, N., Eisman, J. Identification and characterization of a novel human RNA-binding protein. Gene 166: 323-327, 1995. [PubMed: 8543184] [Full Text: https://doi.org/10.1016/0378-1119(95)00571-4]
Burn, T. C., Connors, T. D., Van Raay, T. J., Dackowski, W. R., Millholland, J. M., Klinger, K. W., Landes, G. M. Generation of a transcriptional map for a 700-kb region surrounding the polycystic kidney disease type 1 (PKD1) and tuberous sclerosis type 2 (TSC2) disease genes on human chromosome 16p13.3. Genome Res. 6: 525-537, 1996. [PubMed: 8828041] [Full Text: https://doi.org/10.1101/gr.6.6.525]
Loyer, P., Trembley, J. H., Lahti, J. M., Kidd, V. J. The RNP protein, RNPS1, associates with specific isoforms of the p34(cdc2)-related PITSLRE protein kinase in vivo. J. Cell Sci. 111: 1495-1506, 1998. [PubMed: 9580558] [Full Text: https://doi.org/10.1242/jcs.111.11.1495]
Lykke-Andersen, J., Shu, M.-D., Steitz, J. A. Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1. Science 293: 1836-1839, 2001. [PubMed: 11546874] [Full Text: https://doi.org/10.1126/science.1062786]
Mayeda, A., Badolato, J., Kobayashi, R., Zhang, M. Q., Gardiner, E. M., Krainer, A. R. Purification and characterization of human RNPS1: a general activator of pre-mRNA splicing. EMBO J. 18: 4560-4570, 1999. [PubMed: 10449421] [Full Text: https://doi.org/10.1093/emboj/18.16.4560]
Sakashita, E., Tatsumi, S., Werner, D., Endo, H., Mayeda, A. Human RNPS1 and its associated factors: a versatile alternative pre-mRNA splicing regulator in vivo. Molec. Cell. Biol. 24: 1174-1187, 2004. Note: Erratum: Molec. Cell. Biol. 24: 3068 only, 2004. [PubMed: 14729963] [Full Text: https://doi.org/10.1128/MCB.24.3.1174-1187.2004]