Molecular biology of renin. II: Gene control by messenger RNA, transfection and transgenic studies.

PURPOSE: This review addresses the question of renin gene control by examining information from messenger RNA, transgene, transient expression and DNA-protein binding studies.

CONTENTS: Although information from messenger RNA studies may be reliable for tissues such as kidney and, in mouse, submandibular gland, which have relatively high expression, more sensitive approaches, e.g. polymerase chain reaction technology, are needed for studies of renin gene regulation in other tissues. Control at the molecular level is particularly uncertain, with conflicting data suggesting that renin promoter activity depends either upon a complex interaction of positive and negative regulatory elements or upon the presence of specific trans-acting factor(s) alone, which act upon putative enhancer(s) in the renin-associated DNA. Only after renin-synthesizing cell lines are studied will a clearer picture emerge. Transgenic work has loosely defined the DNA needed as being less than several kilobases of flanking sequences, with the possibility that sequences in the gene itself, particularly in intron 1, are necessary. Such transgenic work has also shown that the renin gene can cause hypertension.

CONCLUSION

Knowledge of DNA and proteins and the interactions that turn on transcription of the renin gene is still rudimentary and currently represents the major challenge in renin research.