The evolution of apolipoprotein B and its mRNA editing complex. Does the lack of editing contribute to hypertriglyceridemia?

The evolution of apolipoprotein B and its mRNA editing complex. Does the lack of editing contribute to hypertriglyceridemia?
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DOI:
10.1016/j.gene.2017.10.024
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发表时间:
2018-01-30
期刊:
影响因子:
3.5
通讯作者:
Lokman, Mark
Lokman, Mark
中科院分区:
生物学3区
文献类型:
--
作者:
Damsteegt, Erin L.;Davie, Andrew;Lokman, Mark

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载脂蛋白B(ApoB)由于在脂质转运过程中的重要作用而受到广泛关注。哺乳动物全长apob 100可以通过载脂蛋白B mRNA编辑酶、催化多肽样复合物1(Apobec 1)进行转录后编辑,产生截短的Apob B,称为Apob 48。虽然全长和截短形式的Apob对于哺乳动物中的正常脂质稳态都很重要,但在哺乳动物分化之前没有证据表明存在apob mRNA编辑,然而,非哺乳动物脊椎动物似乎仅在Apob100的情况下正常发挥功能。到目前为止,在非哺乳类脊椎动物中进行的大部分研究都集中在鸡身上,只有非常有限的数量研究了鱼类中的apob mRNA编辑。本研究的重点是Apobec1和Apob的分子进化,以确定是否apob mRNA编辑发生在鳗鱼,一种基础硬骨鱼,代表了进化上重要的动物群体。没有发现Apobec 1存在或鳗鱼apob被编辑的能力的证据。然而,突变小鼠和非哺乳动物脊椎动物血浆中明显的高脂血症之间存在重要联系。这项研究为帮助弥合鱼类和哺乳动物之间的进化差距提供了必要的证据,并为非哺乳类脊椎动物中缺乏apob mRNA编辑提供了进一步的支持。
The evolution of apolipoprotein B (Apob) has been intensely researched due to its importance during lipid transport. Mammalian full-length apob100 can be post-transcriptionally edited by the enzyme apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like complex-one (Apobec1) resulting in a truncated Apob, known as Apob48. Whilst both full-length and truncated forms of Apob are important for normal lipid homeostasis in mammals, there is no evidence for the presence of apob mRNA editing prior to the divergence of the mammals, yet, non-mammalian vertebrates appear to function normally with only Apob100. To date, the majority of the research carried out in non-mammalian vertebrates has focused on chickens with only a very limited number examining apob mRNA editing in fish. This study focused on the molecular evolution of Apobec1 and Apob in order to ascertain if apob mRNA editing occurs in eels, a basal teleost which represents an evolutionarily important animal group. No evidence for the presence of Apobec1 or the ability for eel apob to be edited was found. However, an important link between mutant mice and the evident hypertriglyceridemia in the plasma of non mammalian vertebrates was made. This study has provided imperative evidence to help bridge the evolutionary gap between fish and mammals and provides further support for the lack of apob mRNA editing in non-mammalian vertebrates.