Disease relevance of RNPS1

• Recombinant human RNPS1 expressed in baculovirus functionally synergizes with SR proteins and strongly activates splicing of both constitutively and alternatively spliced pre-mRNAs [1].

High impact information on RNPS1

• Significantly, RNPS1 triggers NMD when tethered to the 3' untranslated region of beta-globin mRNA, demonstrating its role as a subunit of the postsplicing complex directly involved in mRNA surveillance [2].
• Upon exon ligation, association of RNPS1, UAP56, and SRm160 is destabilized [3].
• We conclude that RNPS1 is not only a potential regulator of alternative splicing but may also play a more fundamental role as a general activator of pre-mRNA splicing [1].
• Biochemical purification of a pre-mRNA splicing activity from HeLa cells that stimulates distal alternative 3' splice sites in a concentration-dependent manner resulted in the identification of RNPS1, a novel general activator of pre-mRNA splicing [1].
• RNPS1 is conserved in metazoans and has an RNA-recognition motif preceded by an extensive serine-rich domain [1].

Biological context of RNPS1

• In contrast, RNAi of CstF-50 in combination with RNPS1 or REFs did not result in an apparent phenotype [4].
• RNPS1 appears to be a versatile factor that regulates alternative splicing of a variety of pre-mRNAs [5].
• To search for factors that functionally interact with RNPS1, we performed a yeast two-hybrid screen with a human cDNA library [5].
• A second EJC protein, RNPS1, also has an ATP-dependent mobility, but SRm300, a protein that binds to SRm160 and participates with it in RNA splicing, remains immobile after ATP supplementation [6].
• Splicing and RNPS1 tethering are shown to enhance the same steps in mRNA biogenesis and function, including mRNA 3' end processing and translation [7].

Anatomical context of RNPS1

• Overexpression of RNPS1 in HeLa cells induced exon skipping in a model beta-globin pre-mRNA and a human tra-2 beta pre-mRNA [5].
• Three of the EJC components, Aly/REF, RNPS1, and SRm160, are found on pre-mRNA by the time the spliceosome is formed, whereas Upf3b associates with splicing intermediates during or immediately after the first catalytic step of the splicing reaction (cleavage of exon 1 and intron-lariat formation) [8].

Physical interactions of RNPS1

• These data indicate that the PITSLRE p110 isoforms interact with RNPS1 in vivo, and that these proteins may in turn influence some aspect of transcriptional and/or splicing regulation [9].
• Nuclear Pnn/DRS protein binds to spliced mRNPs and participates in mRNA processing and export via interaction with RNPS1 [10].

Regulatory relationships of RNPS1

• These results suggest that SRm160 stimulates cleavage independently of its association with EJC components and that the cleavage-stimulatory activity of RNPS1 may be an indirect consequence of its ability to stimulate splicing [4].

Other interactions of RNPS1

• Whereas SRm160 stimulated cleavage to a similar extent in the presence or absence of an active intron, stimulation of 3'-end cleavage by tethered RNPS1 is dependent on an active intron [4].
• The RNP protein, RNPS1, associates with specific isoforms of the p34cdc2-related PITSLRE protein kinase in vivo [9].
• Coexpression of RNPS1 with p54 cooperatively stimulated exon inclusion in an ATP synthase gamma-subunit pre-mRNA [5].
• While Acinus had previously been implicated in apoptosis and was recently identified as a component of the spliceosome, RNPS1 has been described as a general activator of RNA processing [11].

Analytical, diagnostic and therapeutic context of RNPS1

• We propose that RNPS1 is a splicing regulator whose activator function is controlled in part by CK2 phosphorylation [12].
• Interaction of SART3 with RNPS1 through the physical association of N-terminal domains of RNPS1 was confirmed by both in vitro pull-down assay and immunoprecipitation assay [13].

References