Einzeltreffer — DigiBib

We show that a cellular nuclear protein, the SR splicing factor SF2/ASF, controls the level of production of an essential influenza virus protein, the M2 ion channel protein. The M2 mRNA that encodes the ion channel protein is produced by alternative splicing of another viral mRNA, M1 mRNA. The production of M2 mRNA is controlled in two ways. First, a distal (stronger) 5' splice site in M1 mRNA is blocked by the complex of viral polymerase proteins synthesized during infection, allowing the cellular splicing machinery to switch to the proximal (weaker) M2 5' splice site. Second, utilization of the weak M2 5' splice site requires its activation by the cellular SF2/ASF protein. This activation is mediated by the binding of the SF2/ASF protein to a purine-rich splicing enhancer sequence that is located in the 3' exon of M1 mRNA. We demonstrate that activation of the M2 5' splice site is controlled by the SF2/ASF protein in vivo during influenza virus infection. Utilizing four cell lines that differ in their levels of production of the SF2/ASF protein, we show that during virus infection of these cell lines both M2 mRNA and the M2 ion channel protein are produced in amounts that are proportional to the different expression levels of the SF2/ASF protein.

Titel:	Novel exploitation of a nuclear function by influenza virus: the cellular SF2/ASF splicing factor controls the amount of the essential viral M2 ion channel protein in infected cells.
Autor/in / Beteiligte Person:	Shih, SR ; Krug, RM
Zeitschrift:	The EMBO journal, Jg. 15 (1996-10-01), Heft 19, S. 5415-27
Veröffentlichung:	2024- : [London] : Nature Publishing Group ; <i>Original Publication</i>: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-, 1996
Medientyp:	academicJournal
ISSN:	0261-4189 (print)
Schlagwort:	Animals Base Sequence Binding, Competitive Cell Line DNA-Directed RNA Polymerases metabolism Enhancer Elements, Genetic genetics Exons genetics Gene Expression Regulation, Viral genetics Humans Molecular Sequence Data Mutation Protein Binding RNA, Messenger biosynthesis RNA, Messenger genetics RNA, Messenger metabolism RNA, Viral biosynthesis RNA, Viral metabolism RNA-Binding Proteins Serine-Arginine Splicing Factors Viral Matrix Proteins biosynthesis Alternative Splicing physiology Nuclear Proteins metabolism Orthomyxoviridae genetics RNA, Viral genetics Viral Matrix Proteins genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Language: English [EMBO J] 1996 Oct 01; Vol. 15 (19), pp. 5415-27. MeSH Terms: Alternative Splicing / physiology ; Nuclear Proteins / metabolism ; Orthomyxoviridae / genetics ; RNA, Viral / genetics ; Viral Matrix Proteins / *genetics ; Animals ; Base Sequence ; Binding, Competitive ; Cell Line ; DNA-Directed RNA Polymerases / metabolism ; Enhancer Elements, Genetic / genetics ; Exons / genetics ; Gene Expression Regulation, Viral / genetics ; Humans ; Molecular Sequence Data ; Mutation ; Protein Binding ; RNA, Messenger / biosynthesis ; RNA, Messenger / genetics ; RNA, Messenger / metabolism ; RNA, Viral / biosynthesis ; RNA, Viral / metabolism ; RNA-Binding Proteins ; Serine-Arginine Splicing Factors ; Viral Matrix Proteins / biosynthesis References: J Gen Virol. 1984 Jan;65 ( Pt 1):153-64. (PMID: 6546394) ; EMBO J. 1995 Jul 17;14(14):3540-51. (PMID: 7543047) ; J Virol. 1988 Aug;62(8):2762-72. (PMID: 2455818) ; Virology. 1982 Dec;123(2):237-56. (PMID: 6184879) ; J Virol. 1989 Mar;63(3):1265-74. (PMID: 2783738) ; Nature. 1989 Mar 16;338(6212):254-7. (PMID: 2784194) ; Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9. (PMID: 2784208) ; Cell. 1989 Jul 14;58(1):205-14. (PMID: 2752419) ; Cell. 1989 Aug 11;58(3):449-59. (PMID: 2503251) ; Nature. 1990 Mar 29;344(6265):461-3. (PMID: 1690860) ; Cell. 1990 Jul 13;62(1):25-34. (PMID: 2163768) ; Cell. 1990 Jul 13;62(1):35-42. (PMID: 2364434) ; Proc Natl Acad Sci U S A. 1990 Sep;87(18):7160-4. (PMID: 1976252) ; Genes Dev. 1990 Jul;4(7):1158-71. (PMID: 2145194) ; Virology. 1991 Jul;183(1):32-43. (PMID: 2053285) ; Cell. 1991 Jul 26;66(2):383-94. (PMID: 1830244) ; Genes Dev. 1992 Feb;6(2):255-67. (PMID: 1531330) ; Mol Cell Biol. 1992 Mar;12(3):962-70. (PMID: 1532050) ; Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2814-8. (PMID: 1557388) ; Genes Dev. 1992 May;6(5):837-47. (PMID: 1577277) ; Cell. 1992 May 1;69(3):517-28. (PMID: 1374685) ; Nature. 1993 Mar 11;362(6416):171-5. (PMID: 7680770) ; Science. 1993 Apr 9;260(5105):219-22. (PMID: 8385799) ; Cell. 1993 Jul 16;74(1):105-14. (PMID: 8334698) ; Cell. 1995 Aug 11;82(3):485-94. (PMID: 7634337) ; Cell. 1995 Aug 11;82(3):495-506. (PMID: 7634338) ; Nature. 1995 Aug 10;376(6540):530-3. (PMID: 7637788) ; Virology. 1995 Sep 10;212(1):225-31. (PMID: 7676635) ; Virology. 1995 Oct 1;212(2):411-21. (PMID: 7571410) ; Virology. 1995 Nov 10;213(2):373-85. (PMID: 7491762) ; RNA. 1995 Sep;1(7):663-80. (PMID: 7585252) ; RNA. 1995 Oct;1(8):794-806. (PMID: 7493325) ; J Biol Chem. 1993 Jul 25;268(21):15659-66. (PMID: 8340391) ; Nature. 1993 Sep 2;365(6441):82-5. (PMID: 8361546) ; EMBO J. 1993 Sep;12(9):3607-17. (PMID: 8253084) ; Genes Dev. 1993 Dec;7(12A):2405-17. (PMID: 8253386) ; Cell. 1993 Dec 17;75(6):1061-70. (PMID: 8261509) ; Genes Dev. 1993 Dec;7(12B):2598-608. (PMID: 8276242) ; Nucleic Acids Res. 1993 Dec 25;21(25):5803-16. (PMID: 8290338) ; EMBO J. 1994 Feb 1;13(3):704-12. (PMID: 8313914) ; Cell. 1994 Feb 25;76(4):735-46. (PMID: 8124712) ; J Virol. 1994 Apr;68(4):2425-32. (PMID: 7908060) ; Nature. 1994 Mar 10;368(6467):119-24. (PMID: 8139654) ; Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3363-7. (PMID: 7512732) ; Mol Cell Biol. 1994 Nov;14(11):7670-82. (PMID: 7935481) ; J Biol Chem. 1995 Mar 10;270(10):5346-52. (PMID: 7890647) ; Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2642-6. (PMID: 7708698) ; Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6324-8. (PMID: 7541537) ; Cell. 1985 Mar;40(3):627-33. (PMID: 3882238) Grant Information: AI11772 United States AI NIAID NIH HHS Substance Nomenclature: 0 (M-protein, influenza virus) ; 0 (M1 protein, Influenza A virus) ; 0 (M2 protein, Influenza A virus) ; 0 (Nuclear Proteins) ; 0 (RNA, Messenger) ; 0 (RNA, Viral) ; 0 (RNA-Binding Proteins) ; 0 (Viral Matrix Proteins) ; 170974-22-8 (Serine-Arginine Splicing Factors) ; EC 2.7.7.6 (DNA-Directed RNA Polymerases) Entry Date(s): Date Created: 19961001 Date Completed: 19961216 Latest Revision: 20181113 Update Code: 20231215 PubMed Central ID: PMC452284

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Novel exploitation of a nuclear function by influenza virus: the cellular SF2/ASF splicing factor controls the amount of the essential viral M2 ion channel protein in infected cells.