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首页> 外文期刊>Molecular and Cellular Biology >The decline in human Alu retroposition was accompanied by an asymmetric decrease in SRP9/14 binding to dimeric Alu RNA and increased expression of small cytoplasmic Alu RNA.
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The decline in human Alu retroposition was accompanied by an asymmetric decrease in SRP9/14 binding to dimeric Alu RNA and increased expression of small cytoplasmic Alu RNA.

机译：人Alu逆位的下降伴随着SRP9 / 14与二聚体Alu RNA的结合不对称减少以及小细胞质Alu RNA的表达增加。

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Alu interspersed elements are inserted into the genome by a retroposition process that occurs via dimeric Alu RNA and causes genetic disorders in humans. Alu RNA is labile and can be diverted to a stable left monomer transcript known as small cytoplasmic Alu (scAlu) RNA by RNA 3' processing, although the relationship between Alu RNA stability, scAlu RNA production, and retroposition has been unknown. In vivo, Alu and scAlu transcripts interact with the Alu RNA-binding subunit of signal recognition particle (SRP) known as SRP9/14. We examined RNAs corresponding to Alu sequences that were differentially active during primate evolution, as well as an Alu RNA sequence that is currently active in humans. Mutations that accompanied Alu RNA evolution led to changes in a conserved structural motif also found in SRP RNAs that are associated with thermodynamic destabilization and decreased affinity of the Alu right monomer for SRP9/14. In contrast to the right monomer, the Alu left monomer maintained structural integrity and high affinity for SRP9/14, indicating that scAlu RNA has been under selection during human evolution. Loss of Alu right monomer affinity for SRP9/14 is associated with scAlu RNA production from Alu elements in vivo. Moreover, the loss in affinity coincided with decreased rates of Alu amplification during primate evolution. This indicates that stability of the Alu right monomer is a critical determinant of Alu retroposition. These results provide insight into Alu mobility and evolution and into how retroposons may interact with host proteins during genome evolution.
机译：Alu散布的元素通过二聚Alu RNA发生的逆向过程插入基因组，并导致人类遗传疾病。尽管Alu RNA稳定性，scAlu RNA产生和重新定位之间的关系尚不清楚，但Alu RNA不稳定，可以通过RNA 3'加工转移到称为小胞质Alu（scAlu）RNA的稳定的左单体转录物中。在体内，Alu和scAlu转录物与称为SRP9 / 14的信号识别颗粒（SRP）的Alu RNA结合亚基相互作用。我们检查了与在灵长类动物进化过程中具有差异活性的Alu序列相对应的RNA，以及目前在人类中具有活性的Alu RNA序列。伴随Alu RNA进化的突变导致在SRP RNA中也发现了保守结构基序的变化，这与热力学不稳定和Alu右单体对SRP9 / 14的亲和力降低有关。与右单体相反，Alu左单体保持结构完整性和对SRP9 / 14的高亲和力，表明scAlu RNA在人类进化过程中处于选择状态。 Alu对SRP9 / 14的右单体亲和力的丧失与体内Alu元件产生的scAlu RNA有关。此外，亲和力的丧失与灵长类动物进化过程中Alu扩增速率的降低相吻合。这表明Alu右单体的稳定性是Alu重新定位的关键决定因素。这些结果提供了对Alu迁移和进化以及逆转录子在基因组进化过程中如何与宿主蛋白相互作用的见解。

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