Developmental regulation of alternatively spliced acetyl-CoA carboxylase-alpha mRNAs encoding isozymes with or without an eight amino acid domain upstream of the Ser-1200 phosphorylation motif in the mammary gland.
Expression of a variant acetyl-CoA carboxylase-alpha (ACC-alpha) mRNA encoding an isozyme either comprising (+24nt) or lacking (Delta24nt) an eight amino acid domain proximal to the Ser-1200 phosphorylation motif has been investigated in ovine and rat mammary tissue throughout pregnancy and lactation. The ratio of the Delta24nt mRNA: +24nt mRNA in ovine tissues varied from 0.1-0.25 (spleen, lung, muscle, heart, adipose tissue, brain) to 0.6-0.8 (pancreas, liver, kidney) to approximately 5.0 (lactating mammary gland). The sixfold increase in total ACC-alpha mRNA expression in mammary gland during lactation was due entirely to a tenfold increase in the level of the Delta24nt species as the level of expression of the +24nt species remained unaltered between pregnancy and lactation. This mode of expression of the +24nt and Delta24nt mRNAs was similar in rat mammary gland. Between day 20 of pregnancy and day 4 of lactation the ratio of the Delta24nt : +24nt mRNA increased from 2:1 to 10-20:1. Forced involution reduced the ratio of the two mRNAs to levels observed throughout pregnancy. Treatment of lactating rats with bromocryptine reduced the ratio of the Delta24nt : +24nt mRNA to relative levels observed after forced involution, suggesting that the exonic splicing responsible for the generation of the two mRNA isoforms is prolactin responsive.
Barber
M C
MC
Hannah Research Institute, Ayr KA6 5HL, UK.
Pooley
L
L
Travers
M T
MT
D000103:Acetyl-CoA Carboxylase / Q000737:chemistry / Q000235:genetics*; D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D007774:Lactation / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012694:Serine / Q000737:chemistry; D012756:Sheep; D014018:Tissue Distribution
D007527:Isoenzymes; D012333:RNA, Messenger; D012694:Serine; D000103:Acetyl-CoA Carboxylase