Rex-dependent nucleolar accumulation of HTLV-I mRNAs

Abstract

The regulator of virion protein expression (Rex) of the human T-cell leukemia virus type I (HTLV-I) modulates the pattern and level of spliced and unspliced retroviral mRNA species in the cytoplasm. The elucidation of the molecular basis for this regulation is likely to throw light on new regulatory mechanisms of the host cell. We have investigated the possibility that Rex acts to direct unspliced viral RNA to the nucleolus. To test this possibility, we used in situ hybridization to detect HTLV-I envelope protein (env) transcripts formed in the nucleolus in the presence and absence of the Rex protein. The HTLV-I env sequences are normally removed by splicing from the HTLV-I RNA in the absence of Rex. The experiments presented here show that the accumulation of HTLV-I env sequences in the nucleolus is significantly increased in the presence of Rex. The results raise the possibility that Rex directs unspliced viral mRNA to the nucleolus whence it is exported to the cytoplasm for translation. The association between the nucleolus and retroviral mRNA was lost in purified nucleoli after cellular fractionation.