HIV RTC accumulation in the nucleus (top) fails without tRNA (bottom).


HIV rides the tRNA train to the nucleus, according to Lyubov Zaitseva, Richard Myers, and Ariberto Fassati (University College, London, UK).

For HIV to propagate inside cells, it must first enter the nucleus and, using its reverse transcription complex (RTC), integrate into the host genome. Fassati and his team previously showed that a nuclear import protein called importin 7 was partly responsible for HIV RTC transport to the nucleus.

The team has now set about an unbiased task to find other nuclear import factors. Through multiple cell fractionation steps, they identified an RNA component capable of supporting nuclear import of HIV RTC. Sequencing revealed that the component was tRNA. Sure that tRNAs—instrumental for cytoplasmic protein translation—could not be responsible, Fassati thought, “Oh no! It's all wrong, we've got to start all over again.” Only after multiple repetitions was the team convinced that the tRNA was not merely a contaminant.

Virtually all the tRNAs isolated from the active fraction (the one capable of nuclear import) had defective 3′ ends and were thus incapable of supporting translation. Wild-type tRNAs, on the other hand, had very little nuclear import activity.

Fassati speculates that perhaps the defective tRNAs get shuttled back to the nucleus for repair or degradation. Nuclear import costs energy, but the expense is probably worthwhile to ensure undisturbed protein translation. Whatever the host cell's cost, HIV enjoys a free ride.


Zaitseva, L., et al.