LA-AUTOANTIGEN ALLEVIATES TRANSLATIONAL REPRESSION BY THE 5' LEADER SEQUENCE OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MESSENGER-RNA

The trans-activation response element (TAR) at the 5' end of the human immunodeficiency virus type 1 (HIV-1) mRNAs forms a stable hairpin st ructure which is a target for binding of the virally encoded protein T at, which activates viral gene expression, as well as several cellular factors. TAR is also inhibitory to translation. One of several host f actors that binds to TAR RNA is the La autoantigen, an RNA binding pro tein which functions in RNA polymerase III transcription termination a nd has also been implicated in cap-independent internal translation in itiation on poliovirus RNA. Here we show that La autoantigen alleviate s translational repression by the HIV-1 leader RNA. In rabbit reticulo cyte lysate, La relieves the cis-inhibitory effect of the TAR RNA on t ranslation of bacterial chloramphenicol acetyltransferase (CAT) mRNA b ut not inhibition that is mediated by an artificial secondary structur e element. Canonical translation factors exhibited slight (eIF-2 and G EF) or no (eIF-4A, eIF-4B, eIF-4E, eIF-4F, eIF-3, and eEF-1 alpha) sti mulatory activity on translation of TAR-containing CAT mRNA. In additi on, we show that poliovirus RNA, in spite of being an inefficient temp late in rabbit reticulocyte lysate, is a strong competitive inhibitor of translation of TAR-containing CAT mRNA but not CAT mRNA. This inhib ition can be relieved by La but not by any other translation factor. T he results suggest a possible involvement of the La autoantigen in HTV -1 gene expression.