An ADAR that edits transcripts encoding ion channel subunits functions as a dimer
被引:94
作者:
Gallo, A
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Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, ScotlandWestern Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
Gallo, A
[1
]
Keegan, LP
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Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, ScotlandWestern Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
Keegan, LP
[1
]
Ring, GM
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Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, ScotlandWestern Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
Ring, GM
[1
]
O'Connell, MA
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Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, ScotlandWestern Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
O'Connell, MA
[1
]
机构:
[1] Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
ADAR;
dimer;
Drosophila;
ion channels;
RNA editing;
D O I:
10.1093/emboj/cdg327
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
In this report, we establish that Drosophila ADAR (adenosine deaminase acting on RNA) forms a dimer on double-stranded (ds) RNA, a process essential for editing activity. The minimum region required for dimerization is the N-terminus and dsRNA-binding domain 1 (dsRBD1). Single point mutations within dsRBD1 abolish RNA-binding activity and dimer formation. These mutations and glycerol gradient analysis indicate that binding to dsRNA is important for dimerization. However, dimerization can be uncoupled from dsRNA-binding activity, as a deletion of the N-terminus (amino acids 1-46) yields a monomeric ADAR that retains the ability to bind dsRNA but is inactive in an editing assay, demonstrating that ADAR is only active as a dimer. Different isoforms of ADAR with different editing activities can form heterodimers and this can have a significant effect on editing in vitro as well as in vivo. We propose a model for ADAR dimerization whereby ADAR monomers first contact dsRNA; however, it is only when the second monomer binds and a dimer is formed that deamination occurs.
机构:
Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, ScotlandWestern Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
Cáceres, JF
;
Kornblihtt, AR
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机构:Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA
Fierro-Monti, I
;
Mathews, MB
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机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA
机构:
Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, ScotlandWestern Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
Cáceres, JF
;
Kornblihtt, AR
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h-index: 0
机构:Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA
Fierro-Monti, I
;
Mathews, MB
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机构:
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USAUniv Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA