Interaction between retroviral U5 RNA and the TφC loop of the tRNA^Trp primer is required for efficient initiation of reverse transcription

The 5′ end of avian sarcoma and leukosis virus RNA near the primer binding site forms two RNA secondary structures, U5-inverted repeat (U5-IR) and U5-leader stems, which are required for efficient initiation of reverse transcription. Lying between these two secondary structures is a 7-base sequence that can anneal to the TφC loop of the tRNA^Trp primer. Base substitutions in U5 RNA which disrupt this potential interaction result in a defect in the initiation of reverse transcription both in vivo and in vitro. The defect can be complemented in vitro by base substitutions in the primer. The U5 RNA-TφC interaction is also dependent upon the presence of both the U5-IR and the U5-leader structures. These RNA secondary structures and primer interactions are conserved in other type C and D retroviruses, suggesting that there is a common mechanism for the initiation of reverse transcription in all of these retroviruses.