Sarrowa J, Chang D Y, Maraia R J
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mol Cell Biol. 1997 Mar;17(3):1144-51. doi: 10.1128/MCB.17.3.1144.
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.
Alu散布元件通过一种逆转座过程插入基因组，该过程通过二聚体Alu RNA发生，并导致人类遗传疾病。Alu RNA不稳定，可通过RNA 3'加工转化为一种稳定的左单体转录本，即小细胞质Alu（scAlu）RNA，尽管Alu RNA稳定性、scAlu RNA产生与逆转座之间的关系尚不清楚。在体内，Alu和scAlu转录本与信号识别颗粒（SRP）的Alu RNA结合亚基相互作用，该亚基称为SRP9/14。我们研究了与灵长类动物进化过程中差异活跃的Alu序列相对应的RNA，以及目前在人类中活跃的Alu RNA序列。伴随Alu RNA进化的突变导致了SRP RNA中也存在的一个保守结构基序发生变化，该变化与热力学不稳定以及Alu右单体对SRP9/14的亲和力降低有关。与右单体不同，Alu左单体保持结构完整性并对SRP9/14具有高亲和力，这表明scAlu RNA在人类进化过程中受到了选择。Alu右单体对SRP9/14亲和力的丧失与体内Alu元件产生scAlu RNA有关。此外，亲和力的丧失与灵长类动物进化过程中Alu扩增速率的降低同时发生。这表明Alu右单体的稳定性是Alu逆转座的关键决定因素。这些结果为Alu的移动性和进化以及逆转座子在基因组进化过程中如何与宿主蛋白相互作用提供了见解。
