tRNALys3: The Primer tRNA for Reverse Transcription in HIV‐1

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Abstract
During the assembly of HIV‐1, tRNA Lys isoacceptors are selectively packaged into the virion, and one of these, tRNA Lys3, is annealed to the viral RNA genome where it acts to prime the reverse transcriptase (RT)‐catalyzed synthesis of viral DNA. We review herein what is known about the selective packaging and annealing of primer tRNA Lys3 . Current evidence suggests that a complex of two major precursor viral proteins, Pr55 gag and Pr160 gag‐pol, interact with a tRNA Lys /lysyl‐tRNA synthetase (LysRS) complex during viral assembly, with Pr55 gag interacting with both LysRS and Pr160 gag‐pol, and RT sequences within Pr160 gag‐pol binding to tRNA Lys . LysRS appears to target the tRNA Lys isoacceptors for incorporation into HIV‐1. In the virion, the 3' terminal 18 nucleotides of tRNA Lys3 anneals to an 18‐nucleotide sequence at the 5' terminal region of viral RNA termed the primer binding site (PBS). Evidence is presented that other regions on the tRNA Lys3 also anneal with other regions in viral RNA upstream of the PBS, resulting in a destabilized tRNA Lys3 structure. Both viral and tRNA Lys3 regions need to be denatured to establish annealing, and the roles of both viral and cellular proteins in this process are discussed.

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