Differential splicing yields novel adenovirus 5 E1A mRNAs that encode 30 kd and 35 kd proteins

In addition to the protein products of the adenovirus E1A 13S and 12S mRNAs, monoclonal antibodies specific for the E1A proteins immunoprecipitate polypeptides with relative mol. wt of 30,000 (30 kd) and 35,000 (35 kd) from extracts of infected cells. The 30 kd and 35 kd proteins are encoded by novel mRNAs referred to as the 10S and 11S mRNAs, respectively. These two mRNAs arise from differential splicing of the E1A precursor RNA. For the 10S mRNA, the precursor is spliced twice, once removing the region between nucleotides 637 and 854 and once between 974 and 1229. The splice between nucleotides 974 and 1229 is identical to the one used for the processing of the 12S mRNA. Synthesis of the 11S mRNA also utilizes two splicing events. One of these is identical to the 637/854 splice of the 10S mRNA, and the other removes the region between nucleotides 1112 and 1229, a splice junction also found in the 13S mRNA. All four mRNAs used the same reading frame and, therefore, code for related proteins. The products of the 10S and 11S mRNAs are identical to the products of the 12S and 13S mRNAs, respectively, except for an internal stretch of 27 amino acids removed by the 637/854 splice. Within this segment is a group of amino acid residues that is highly conserved between different adenovirus serotypes. Mutant adenoviruses in which the wild-type E1A sequences have been replaced with cDNA copies of the 10S or 11S mRNAs are defective for growth on HeLa cells suggesting that this region is important for viral growth.(ABSTRACT TRUNCATED AT 250 WORDS)