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/

Alu interspersed elements are inserted into the genome by a retroposit ion process that occurs via dimeric Alu RNA and causes genetic disorde rs in humans, Alu RNA is labile and can be diverted to a stable left m onomer transcript known as small cytoplasmic AB (scAlu) RNA by RNA 3' processing, although the relationship between Alu RNA stability, scAlu RNA production, and retroposition has been unknown, In vivo, Aln and scAlu transcripts interact with the Alu RNA-binding subunit of signal recognition particle (SRP) known as SRP9/14. We examined RNAs correspo nding 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 associat ed with thermodynamic destabilization and decreased affinity of the Al u right monomer for SRP9/14. In contrast to the right monomer, the Alu left monomer maintained structural integrity and high affinity for SR P9/14, indicating that scAlu RNA has been under selection during human evolution, Loss of Alu right monomer affinity for SRP9/14 is associat ed with scAlu RNA production from Alu elements in vivo. Moreover, the loss in affinity coincided with decreased rates of Alu amplification d uring primate evolution, This indicates that stability of the Alu righ t monomer is a critical determinant of Alu retroposition. These result s provide insight into Alu mobility and evolution and into how retropo sons may interact with host proteins during genome evolution.