Regulated splicing of adenovirus type 5 E4 transcripts and regulated cytoplasmic accumulation of E4 mRNA.

The E4 gene of human type C adenoviruses has been shown previously to give rise to an array of mRNAs via differential splicing. In this study, the pattern of expression of these mRNAs during lytic infection was examined, and two distinct temporal classes were defined. mRNAs of the early class were distinguished from those of the late class by the presence, in the early class, of a sequence in the 3' half of the mRNA that was removed as an intron in the late class. A single mRNA of the late class was found to show a strong dependence on the presence of the 55-kDa protein from region E1b and the open reading frame 6 protein from region E4 for its normal cytoplasmic accumulation. One feature of this mRNA that distinguishes it from other E4 mRNAs expressed at late times is the retention within it of an intron from the 5' half of E4; it may therefore be recognized as incompletely spliced by the host cell and retained in the nucleus. It is proposed that the E1b 55-kDa/E4 open reading frame 6 protein complex facilitates accumulation of this mRNA by overcoming this retention mechanism.