AID can restrict L1 retrotransposition suggesting a dual role in innate and adaptive immunity.
AID can restrict L1 retrotransposition suggesting a dual role in innate and adaptive immunity.
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DOI：
10.1093/nar/gkp030
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发表时间：
2009-04
影响因子：
14.9
通讯作者：
Harris RS
中科院分区：
文献类型：
--
作者：
MacDuff DA;Demorest ZL;Harris RS
逆转录转座子占哺乳动物基因组的40%以上。一些拷贝仍然能够移动，新的插入促进遗传变异。DNA胞嘧啶脱氨酶的APOBEC3家族的几个成员的功能是限制各种逆转录元件的复制，例如含有长末端重复序列（LTR）的MusD和Ty1元件，以及非LTR逆转录转座子L1和Alu。然而，APOBEC3基因仅限于哺乳动物谱系，而反转录转座子则广泛得多。这就提出了一个问题，即在缺乏APOBEC3基因的物种中，什么样的细胞因子控制逆转录元件转座。一个强有力的系统发育的情况下，可以作出的祖先激活诱导脱氨酶（AID）样基因复制和分歧，以根APOBEC3谱系在哺乳动物。因此，我们测试了当今AID蛋白具有抗逆转录酶活性的假设。我们发现，AID可以抑制反转录转座的L1通过DNA脱氨基的独立机制。这一机制可能表现在细胞质区室共同或postconflictionally。与卵巢中AID表达的证据一起，我们的数据结合起来表明，AID除了在创造抗体多样性中发挥不可或缺的作用外，还具有先天免疫功能。
Retrotransposons make up over 40% of the mammalian genome. Some copies are still capable of mobilizing and new insertions promote genetic variation. Several members of the APOBEC3 family of DNA cytosine deaminases function to limit the replication of a variety of retroelements, such as the long-terminal repeat (LTR)-containing MusD and Ty1 elements, and that of the non-LTR retrotransposons, L1 and Alu. However, the APOBEC3 genes are limited to mammalian lineages, whereas retrotransposons are far more widespread. This raises the question of what cellular factors control retroelement transposition in species that lack APOBEC3 genes. A strong phylogenetic case can be made that an ancestral activation-induced deaminase (AID)-like gene duplicated and diverged to root the APOBEC3 lineage in mammals. Therefore, we tested the hypothesis that present-day AID proteins possess anti-retroelement activity. We found that AID can inhibit the retrotransposition of L1 through a DNA deamination-independent mechanism. This mechanism may manifest in the cytoplasmic compartment co- or posttranslationally. Together with evidence for AID expression in the ovary, our data combined to suggest that AID has innate immune functions in addition to its integral roles in creating antibody diversity.
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DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
8
作者：
Endo, Y.;Marusawa, H.;Chiba, T.
通讯作者：
Chiba, T.
影响因子：
9.8
作者：
Brouha, B;Meischl, C;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
64.8
作者：
Esnault, C;Heidmann, O;Schwartz, O
通讯作者：
Schwartz, O
影响因子：
64.8
作者：
Chiu, YL;Soros, VB;Greene, WC
通讯作者：
Greene, WC