| Structural highlights
Function
[RNPS1_HUMAN] Part of pre- and post-splicing multiprotein mRNP complexes. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Enhances the formation of the ATP-dependent A complex of the spliceosome. Involved in both constitutive splicing and, in association with SRP54 and TRA2B/SFRS10, in distinctive modulation of alternative splicing in a substrate-dependent manner. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Participates in mRNA 3'-end cleavage. Involved in UPF2-dependent nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Also mediates increase of mRNA abundance and translational efficiency. Binds spliced mRNA 20-25 nt upstream of exon-exon junctions.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [SAP18_MOUSE] Component of the SIN3-repressing complex. Enhances the ability of SIN3-HDAC1-mediated transcriptional repression. When tethered to the promoter, it can direct the formation of a repressive complex to core histone proteins. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit mRNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits the formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function (By similarity).
Publication Abstract from PubMed
The ASAP complex interacts with the exon-junction complex (EJC), a messenger ribonucleoprotein complex involved in post-transcriptional regulation. The three ASAP subunits (Acinus, RNPS1 and SAP18) have been individually implicated in transcriptional regulation, pre-mRNA splicing and mRNA quality control. To shed light on the basis for and consequences of ASAP's interaction with the EJC, we have determined the 1.9-A resolution structure of a eukaryotic ASAP core complex. The RNA-recognition motif of RNPS1 binds to a conserved motif of Acinus with a recognition mode similar to that observed in splicing U2AF proteins. The Acinus-RNPS1 platform recruits the ubiquitin-like domain of SAP18, forming a ternary complex that has both RNA- and protein-binding properties. Unexpectedly, our structural analysis identified an Acinus-like motif in Pinin, another EJC-associated splicing factor. We show that Pinin physically interacts with RNPS1 and SAP18, forming an alternative ternary complex, PSAP.
The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex.,Murachelli AG, Ebert J, Basquin C, Le Hir H, Conti E Nat Struct Mol Biol. 2012 Mar 4;19(4):378-86. doi: 10.1038/nsmb.2242. PMID:22388736[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mayeda A, Badolato J, Kobayashi R, Zhang MQ, Gardiner EM, Krainer AR. Purification and characterization of human RNPS1: a general activator of pre-mRNA splicing. EMBO J. 1999 Aug 16;18(16):4560-70. PMID:10449421 doi:http://dx.doi.org/10.1093/emboj/18.16.4560
- ↑ Lykke-Andersen J, Shu MD, Steitz JA. Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1. Science. 2001 Sep 7;293(5536):1836-9. PMID:11546874 doi:http://dx.doi.org/10.1126/science.1062786
- ↑ Schwerk C, Prasad J, Degenhardt K, Erdjument-Bromage H, White E, Tempst P, Kidd VJ, Manley JL, Lahti JM, Reinberg D. ASAP, a novel protein complex involved in RNA processing and apoptosis. Mol Cell Biol. 2003 Apr;23(8):2981-90. PMID:12665594
- ↑ McCracken S, Longman D, Johnstone IL, Caceres JF, Blencowe BJ. An evolutionarily conserved role for SRm160 in 3'-end processing that functions independently of exon junction complex formation. J Biol Chem. 2003 Nov 7;278(45):44153-60. Epub 2003 Aug 27. PMID:12944400 doi:http://dx.doi.org/10.1074/jbc.M306856200
- ↑ 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. Mol Cell Biol. 2004 Feb;24(3):1174-87. PMID:14729963
- ↑ Nott A, Le Hir H, Moore MJ. Splicing enhances translation in mammalian cells: an additional function of the exon junction complex. Genes Dev. 2004 Jan 15;18(2):210-22. PMID:14752011 doi:http://dx.doi.org/10.1101/gad.1163204
- ↑ Trembley JH, Tatsumi S, Sakashita E, Loyer P, Slaughter CA, Suzuki H, Endo H, Kidd VJ, Mayeda A. Activation of pre-mRNA splicing by human RNPS1 is regulated by CK2 phosphorylation. Mol Cell Biol. 2005 Feb;25(4):1446-57. PMID:15684395 doi:http://dx.doi.org/25/4/1446
- ↑ Gehring NH, Kunz JB, Neu-Yilik G, Breit S, Viegas MH, Hentze MW, Kulozik AE. Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol Cell. 2005 Oct 7;20(1):65-75. PMID:16209946 doi:http://dx.doi.org/S1097-2765(05)01554-6
- ↑ Viegas MH, Gehring NH, Breit S, Hentze MW, Kulozik AE. The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway. Nucleic Acids Res. 2007;35(13):4542-51. Epub 2007 Jun 22. PMID:17586820 doi:http://dx.doi.org/gkm461
- ↑ Michelle L, Cloutier A, Toutant J, Shkreta L, Thibault P, Durand M, Garneau D, Gendron D, Lapointe E, Couture S, Le Hir H, Klinck R, Elela SA, Prinos P, Chabot B. Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators. Mol Cell Biol. 2012 Mar;32(5):954-67. doi: 10.1128/MCB.06130-11. Epub 2011 Dec, 27. PMID:22203037 doi:http://dx.doi.org/10.1128/MCB.06130-11
- ↑ Murachelli AG, Ebert J, Basquin C, Le Hir H, Conti E. The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex. Nat Struct Mol Biol. 2012 Mar 4;19(4):378-86. doi: 10.1038/nsmb.2242. PMID:22388736 doi:10.1038/nsmb.2242
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