Role of purine-rich exonic splicing enhancers in nuclear retention of pre-mRNAs.
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.
Taniguchi
Ichiro
I
Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Masuyama
Kaoru
K
Ohno
Mutsuhito
M
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
D011687:Purines; D012322:RNA Precursors; C030985:purine
J Biol Chem. 2004 Jul 23;279(30):31745-9
15184380
Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9666-70
15210956
Cell. 1989 May 19;57(4):573-83
2655924
Cell. 1989 Dec 1;59(5):789-95
2686839
Mol Cell Biol. 1990 Jan;10(1):84-94
2136768
Genes Dev. 1993 Dec;7(12B):2598-608
8276242
Mol Cell Biol. 1994 Feb;14(2):1347-54
8289812
Curr Opin Genet Dev. 1996 Apr;6(2):215-20
8722179
EMBO J. 1997 Apr 1;16(7):1759-71
9130720
Cell. 1998 Apr 3;93(1):139-48
9546399
Nucleic Acids Res. 1999 Sep 1;27(17):3455-65
10446233
Mol Cell. 2004 Nov 5;16(3):363-73
15525510
EMBO J. 2004 Dec 8;23(24):4847-56
15565172
Curr Opin Cell Biol. 2005 Jun;17(3):287-93
15901499
Curr Opin Cell Biol. 2005 Jun;17(3):294-301
15901500
Curr Opin Cell Biol. 2005 Jun;17(3):302-8
15901501
Mol Cell. 2005 Nov 11;20(3):413-25
16285923
Cell. 2006 Jun 16;125(6):1041-53
16777596
Mol Cell. 2006 Jun 23;22(6):769-81
16793546
Cell. 2006 Dec 29;127(7):1389-400
17190602
Biochem Biophys Res Commun. 2007 Aug 3;359(3):580-5
17548051
Trends Biochem Sci. 2000 Mar;25(3):106-10
10694877
EMBO J. 2000 Apr 17;19(8):1873-86
10775271
Trends Biochem Sci. 2000 Aug;25(8):381-8
10916158
EMBO J. 2001 Apr 17;20(8):2062-8
11296238
Mol Cell. 2001 Apr;7(4):899-905
11336712
EMBO J. 2001 Sep 3;20(17):4987-97
11532962
Mol Cell. 2002 Mar;9(3):659-71
11931772
Nat Rev Genet. 2002 Apr;3(4):285-98
11967553
Nature. 2002 May 16;417(6886):304-8
11979277
Annu Rev Biochem. 2002;71:375-403
12045101
Science. 2002 Aug 9;297(5583):1007-13
12114529
RNA. 2002 Oct;8(10):1233-41
12403462
Mol Cell. 2003 Mar;11(3):837-43
12667464
Trends Biochem Sci. 2003 Aug;28(8):419-24
12932730
Cell. 2004 Jan 9;116(1):63-73
14718167
Mol Cell. 2004 Jan 30;13(2):201-12
14759366
Genes Cells. 2004 Feb;9(2):121-30
15009090
Curr Opin Cell Biol. 2004 Jun;16(3):285-92
15145353
Curr Opin Struct Biol. 2004 Jun;14(3):335-43
15193314
Genes Dev. 2004 Sep 1;18(17):2074-85
15314030