Nonconservative utilization of aldolase A alternative promoters

• Published in: The Journal of biological chemistry 1990-07, Vol.265 (20), p.11773-11782
• Main Authors: STAUFFER, J. K, COLBERT, M. C, CIEJEK-BAEZ, E
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Cloning, Molecular; Exons; Fructose-Bisphosphate Aldolase - genetics; Fundamental and applied biological sciences. Psychology; Genes; Humans; Isoenzymes - genetics; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Muscles - enzymology; Promoter Regions, Genetic; Rats; Restriction Mapping; RNA Splicing; RNA, Messenger - genetics; Sequence Homology, Nucleic Acid; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)38465-0

Recently, analysis of the sequence and expression of the human aldolase A gene revealed the unique arrangement of three tandem promoters and exons preceding a common coding sequence. A muscle-specific promoter (M) and two flanking widely used promoters (N and H) produce mRNA species which, in their mature forms, differ only in the sequence of their 5'-untranslated regions. We have isolated and investigated the expression of a mouse aldolase A gene. This mouse gene represents a functional gene by sequence analysis, recombinational screening, and by transfection into C2C12 cells. Although there is a high degree of sequence similarity between the mouse and the human gene in the region of the alternative first exons, we have been unable to detect a functional utilization of the 5'-most promoter (N) in the mouse. Steady state mRNAs isolated from a variety of adult tissues and cultured cells were analyzed by RNase protection and primer extension to identify first exon utilization. Consistent with previous reports, exon M is found only in skeletal muscle and exon H, the "housekeeping" exon, is utilized in every tissue where aldolase A is expressed. Under identical conditions we fail to see any evidence of the N exon. Therefore, although sequence homology exists between rodents and primates in the N region, the absence of selective pressure to preserve its primate pattern of expression may have resulted in functional promoter extinction.