Sequences of mRNAs derived from genome RNA segment 7 of influenza virus: colinear and interrupted mRNAs code for overlapping proteins.

Abstract

RNA segment 7 of the influenza A virus genome codes for at least 2 proteins, M1 and M2, which are synthesized from separate mRNA species. Sequence analysis of the M2 mRNA showed that it contains an interrupted sequence of 689 nucleotides. The .apprx. 51 virus-specific nucleotides comprising the 5''-end leader sequence of the M2 mRNA are the same as those found at the 5'' end of the colinear M1 mRNA. Following the leader sequence of the M2 mRNA, there is a 271-nucleotide body region that is 3'' coterminal with the M1 mRNA. Another small potential mRNA (mRNA3) related to RNA segment 7 was found. mRNA3 has a leader sequence of .apprx. 11 virus-specific nucleotides that are the same as the 5'' end of the M1 and M2 mRNA, followed by an interrupted sequence of 729 nucleotides and then a body region of .apprx. 271 nucleotides that is the same as the M2 mRNA. The nucleotide sequences found at the junctions of the interrupted sequences in M2 mRNA and mRNA3 are similar to those found at the splicing points of intervening sequences in eukaryotic mRNA. Both mRNA contain 10-15 heterogeneous nonviral nucleotides at their 5'' ends that appear to be derived from cellular RNA used for priming the transcription of viral RNA. Because the 5''-end sequences of the M1 mRNA and the M2 mRNA are the same and share the 5''-proximal initiation codon for protein synthesis, the first 9 amino acids would be the same in the M1 and M2 protein and then the sequences would diverge. The .apprx. 271-nucleotide body region of the M2 mRNA can be translated in the +1 reading frame and the sequence indicates that M1 and M2 overlap by 14 amino acids. The coding potential of the mRNA3 is for only 9 amino acids and these would be identical to the COOH-terminal region of the membrane protein (M1).