Two distinct species of human growth hormone-variant mRNA in the human placenta predict the expression of novel growth hormone proteins.
We have sought direct evidence for the in vivo expression of the human growth hormone-variant (hGH-V) gene by screening a placental cDNA library with a hGH-V-specific oligonucleotide. Nine independent hGH-V cDNA clones were isolated and analyzed, and three distinct species were detected. Five of these hGH-V cDNAs represent mRNAs spliced and processed in a pattern analogous to that of the highly homologous human growth hormone and human chorionic somatomammotropin gene transcripts. Each of the remaining four hGH-V cDNAs contains an additional segment of 253 nucleotides corresponding in position and sequence to the fourth intron of the hGH-V gene. In addition, one of the mRNAs in this second group uses an alternative downstream polyadenylation site. The alternatively spliced hGH-V mRNA, which we refer to as hGH-V2 mRNA, constitutes approximately 30% of the hGH-V transcripts both in the human term placenta and in a stable mouse fibroblast line expressing the transfected hGH-V gene. The placental expression of the hGH-V gene is specific to villous tissue. The hGH-V2 mRNA is predicted to encode a protein which substitutes the 65 carboxyl-terminal amino acids of hGH-V with a new 104-residue carboxyl terminus resulting in significant divergence in their relative physical properties. The alternative splicing of the hGH-V transcripts to hGH-V and hGH-V2 mRNAs expands the potential complexity of the hGH-V gene's role in normal placental function.
Cooke
N E
NE
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Ray
J
J
Emery
J G
JG
Liebhaber
S A
SA
D000595:Amino Acid Sequence; D001483:Base Sequence; D006063:Chorionic Gonadotropin / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005260:Female; D005796:Genes; D014644:Genetic Variation; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic
D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D013006:Growth Hormone; D004247:DNA