A mammalian RNA editing enzyme

A mammalian RNA editing enzyme
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DOI:
10.1038/379460a0
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发表时间:
1996-02-01
期刊:
影响因子:
64.8
通讯作者:
Higuchi, M
Higuchi, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Melcher, T;Maas, S;Higuchi, M

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通过位点选择性腺苷脱氨作用编辑RNA(1)改变脑表达的谷氨酸受体(GluR)亚单位前信使RNA中的密码子(2-4),包括GluR-B中通道决定簇(Q/R位点)的密码子,其控制α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)受体的Ca 2+渗透性(5,6)。GluR前体mRNA的编辑需要由外显子和内含子序列形成的双链RNA(dsRNA)结构(4,7),并由未知的dsRNA腺苷脱氨酶催化。在这里,我们报告的互补DNA的克隆RED 1,dsRNA腺苷脱氨酶在脑和外周组织中表达,有效地编辑在GluR-B前mRNA的Q/R位点在体外。该位点被DRDA编辑得很差,它与RED 1序列有较远的相关性。这两种脱氨酶编辑GluR-B前mRNA中的R/G位点,表明新兴基因家族的成员催化核转录物中的腺苷脱氨,具有不同但重叠的底物特异性。
EDITING of RNA(1) by site-selective adcnosine deamination alters codons in brain-expressed pre-messenger RNAs for glutamate receptor (GluR) subunits(2-4) including a codon for a channel determinant (Q/R site) in GluR-B, which controls the Ca2+ permeability of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors(5,6). Editing of GluR pre-mRNAs requires a double-stranded RNA (dsRNA) structure formed by esonic and intronic sequences(4,7) and is catalysed by an unknown dsRNA adenosine deaminase. Here we report the cloning of complementary DNA for RED1, a dsRNA adenosine deaminase expressed in brain and peripheral tissues that efficiently edits the Q/R site in GluR-B pre-mRNA in vitro. This site is poorly edited by DRADA, which is distantly sequence related to RED1. Both deaminases edit the R/G site in GluR-B pre-mRNA, indicating that members of an emerging gene family catalyse adenosine deamination in nuclear transcripts with distinct but overlapping substrate specificities.