title: Role of purine-rich exonic splicing enhancers in nuclear retention of pre-mRNAs.
abstract: Intron-containing pre-mRNAs are normally retained in the nucleus until they are spliced to produce mature mRNAs that are exported to the cytoplasm. Although the detailed mechanism is not well understood, the formation of splicing-related complexes on pre-mRNAs is thought to be responsible for the nuclear retention. Therefore, pre-mRNAs containing suboptimal splice sites should tend to leak out to the cytoplasm. Such pre-mRNAs often contain purine-rich exonic splicing enhancers (ESEs) that stimulate splicing of the adjacent intron. Here, we show that ESEs per se possess an activity to retain RNAs in the nucleus through a saturable nuclear retention factor. Cross-competition experiments revealed that intron-containing pre-mRNAs (without ESEs) used the same saturable nuclear retention factor as ESEs. Interestingly, although intronless mRNAs containing ESEs were also poorly exported, spliced mRNAs produced from ESE-containing pre-mRNAs were efficiently exported to the cytoplasm. Thus, the splicing reaction can reset the nuclear retention state caused by ESEs, allowing nuclear export of mature mRNAs. Our results reveal a novel aspect of ESE activity that should contribute to gene expression and RNA quality control.
authors: Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors: Ichiro
authors: I
authors: Taniguchi
authors: Kaoru
authors: K
authors: Masuyama
authors: Mutsuhito
authors: M
authors: Ohno
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D011687:Purines / Q000378:metabolism*; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D014982:Xenopus laevis / Q000235:genetics
chemical_list: D011687:Purines; D012322:RNA Precursors; C030985:purine
references: J Biol Chem. 2004 Jul 23;279(30):31745-9
references: 15184380
references: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9666-70
references: 15210956
references: Cell. 1989 May 19;57(4):573-83
references: 2655924
references: Cell. 1989 Dec 1;59(5):789-95
references: 2686839
references: Mol Cell Biol. 1990 Jan;10(1):84-94
references: 2136768
references: Genes Dev. 1993 Dec;7(12B):2598-608
references: 8276242
references: Mol Cell Biol. 1994 Feb;14(2):1347-54
references: 8289812
references: Curr Opin Genet Dev. 1996 Apr;6(2):215-20
references: 8722179
references: EMBO J. 1997 Apr 1;16(7):1759-71
references: 9130720
references: Cell. 1998 Apr 3;93(1):139-48
references: 9546399
references: Nucleic Acids Res. 1999 Sep 1;27(17):3455-65
references: 10446233
references: Mol Cell. 2004 Nov 5;16(3):363-73
references: 15525510
references: EMBO J. 2004 Dec 8;23(24):4847-56
references: 15565172
references: Curr Opin Cell Biol. 2005 Jun;17(3):287-93
references: 15901499
references: Curr Opin Cell Biol. 2005 Jun;17(3):294-301
references: 15901500
references: Curr Opin Cell Biol. 2005 Jun;17(3):302-8
references: 15901501
references: Mol Cell. 2005 Nov 11;20(3):413-25
references: 16285923
references: Cell. 2006 Jun 16;125(6):1041-53
references: 16777596
references: Mol Cell. 2006 Jun 23;22(6):769-81
references: 16793546
references: Cell. 2006 Dec 29;127(7):1389-400
references: 17190602
references: Biochem Biophys Res Commun. 2007 Aug 3;359(3):580-5
references: 17548051
references: Trends Biochem Sci. 2000 Mar;25(3):106-10
references: 10694877
references: EMBO J. 2000 Apr 17;19(8):1873-86
references: 10775271
references: Trends Biochem Sci. 2000 Aug;25(8):381-8
references: 10916158
references: EMBO J. 2001 Apr 17;20(8):2062-8
references: 11296238
references: Mol Cell. 2001 Apr;7(4):899-905
references: 11336712
references: EMBO J. 2001 Sep 3;20(17):4987-97
references: 11532962
references: Mol Cell. 2002 Mar;9(3):659-71
references: 11931772
references: Nat Rev Genet. 2002 Apr;3(4):285-98
references: 11967553
references: Nature. 2002 May 16;417(6886):304-8
references: 11979277
references: Annu Rev Biochem. 2002;71:375-403
references: 12045101
references: Science. 2002 Aug 9;297(5583):1007-13
references: 12114529
references: RNA. 2002 Oct;8(10):1233-41
references: 12403462
references: Mol Cell. 2003 Mar;11(3):837-43
references: 12667464
references: Trends Biochem Sci. 2003 Aug;28(8):419-24
references: 12932730
references: Cell. 2004 Jan 9;116(1):63-73
references: 14718167
references: Mol Cell. 2004 Jan 30;13(2):201-12
references: 14759366
references: Genes Cells. 2004 Feb;9(2):121-30
references: 15009090
references: Curr Opin Cell Biol. 2004 Jun;16(3):285-92
references: 15145353
references: Curr Opin Struct Biol. 2004 Jun;14(3):335-43
references: 15193314
references: Genes Dev. 2004 Sep 1;18(17):2074-85
references: 15314030