Multiple effects govern endogenous retrovirus survival patterns in human gene introns.
Multiple effects govern endogenous retrovirus survival patterns in human gene introns.
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多种影响控制人基因内含子中内源性逆转录病毒的存活模式。
DOI：
10.1186/gb-2006-7-9-r86
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发表时间：
2006
期刊：
影响因子：
12.3
通讯作者：
Mager, Dixie L.
中科院分区：
文献类型：
--
作者：
van de Lagemaat, Louie N.;Medstrand, Patrik;Mager, Dixie L.
对人类内源性逆转录病毒家族的分析表明，在年轻的内含子逆转录病毒中，基因转录的反义方向的剪接受到抑制。内源性逆转录病毒（ERVs）和孤立的长末端重复序列（LTRs）有一个显着的反义偏置时，位于基因内含子，这表明强大的负选择压力，这些元件在相同的转录方向为封闭基因取向。有人认为，这种偏见反映了LTR内存在强烈的转录调控信号，但很少有工作已经做了进一步调查这一现象。在这里报道的分析中，我们发现个体人类ERV家族在基因内的患病率和反义偏倚程度方面存在显着差异，并表明，无论方向如何，大多数家族的ERV不太可能在内含子中发现，而不是在基因间区域。ERVs跨转录单位的密度分布和存在于共有ERVs中的转录信号的检查表明剪接受体位点连同剪接供体和多聚腺苷酸化信号作为针对大多数ERVs/LTR家族的选择的主要靶标的重要性。此外，对涉及ERV序列的注释的人mRNA剪接事件的分析揭示，相对年轻的人ERV（HERV），HERV 9和HERV-K（HML-2），在基因转录的反义方向时根本不涉及人mRNA剪接事件，而转录区域中有义方向的元件显示出对于使用强剪接位点的相当大的偏好。我们的观察结果表明，年轻的内含子ERVs定向反义基因转录的剪接抑制，这可能是他们的致突变性降低和较高的固定率在基因内含子。
An analysis of human endogenous retrovirus families suggests suppression of splicing among young intronic retroviruses oriented antisense to gene transcription. Endogenous retroviruses (ERVs) and solitary long terminal repeats (LTRs) have a significant antisense bias when located in gene introns, suggesting strong negative selective pressure on such elements oriented in the same transcriptional direction as the enclosing gene. It has been assumed that this bias reflects the presence of strong transcriptional regulatory signals within LTRs but little work has been done to investigate this phenomenon further. In the analysis reported here, we found significant differences between individual human ERV families in their prevalence within genes and degree of antisense bias and show that, regardless of orientation, ERVs of most families are less likely to be found in introns than in intergenic regions. Examination of density profiles of ERVs across transcriptional units and the transcription signals present in the consensus ERVs suggests the importance of splice acceptor sites, in conjunction with splice donor and polyadenylation signals, as the major targets for selection against most families of ERVs/LTRs. Furthermore, analysis of annotated human mRNA splicing events involving ERV sequence revealed that the relatively young human ERVs (HERVs), HERV9 and HERV-K (HML-2), are involved in no human mRNA splicing events at all when oriented antisense to gene transcription, while elements in the sense direction in transcribed regions show considerable bias for use of strong splice sites. Our observations suggest suppression of splicing among young intronic ERVs oriented antisense to gene transcription, which may account for their reduced mutagenicity and higher fixation rate in gene introns.
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影响因子：
4.5
作者：
Maksakova IA;Romanish MT;Gagnier L;Dunn CA;van de Lagemaat LN;Mager DL
通讯作者：
Mager DL
影响因子：
4.1
作者：
Carcedo, MT;Iglesias, JM;Fernandez, MP
通讯作者：
Fernandez, MP
影响因子：
64.5
作者：
PANET, A;CEDAR, H
通讯作者：
CEDAR, H
影响因子：
5.4
作者：
Barr, SD;Leipzig, J;Bushman, FD
通讯作者：
Bushman, FD
影响因子：
14.9
作者：
Pruitt KD;Tatusova T;Maglott DR
通讯作者：
Maglott DR