RNA METABOLISM IN DEVELOPMENT AND HORMONAL REGULATION

提出的研究重点是阐明在这一过程中起作用的机制

The proposed research focuses on elucidating mechanisms operative in the regulation of gene expression during normal development and hormone-induced growth transitions, emphasizing the transaction from quiescence to proliferation. The gene systems to be investigated are 1) selected abundant poly(A) mRNAs which are regulated (i.e. change up to 100-fold in concentration) during normal development and hormone-induced tissue proliferation and 2) rRNA the synthesis of which is rapidly and dramatically altered during these same growth transitions. The studies will encompass 1) experiments designed to elucidate the mechanism(s) by which the concentration of these hormone-responsive abundant poly(A) mRNAs is regulated and 2) and an analysis of the control of RNA polymerase I activity. Cloned cDNAs homologous to these abundant mRNAs will be used as hybridization probes to assess the contribution of altered rates of synthesis, processing and/or turnover to the dramatic change in concentration of the individual mRNAs, some of which increase and others which decrease in response to hormone treatment. The structure/organization of genomic clones of some of these auxin-responsive gene sequences will be investigated. Isolated nucleoli and a reconstituted system (including defined cloned rDNA templates, purified RNA polymerase I, and various crude and/or purified cellular extracts) will be used in studies directed to an analysis of the mechanisms operative in the extensive modulation of RNA polymerase I activity which occurs during various normal and hormone-induced growth transitions, emphasizing the transition to abnormal tissue proliferation. Factors which effect specific initiation and transcription of rRNA chains and which modulate the rate of transcription by engaged RNA polymerase I molecules will be sought and their status in quiescent and proliferating tissues investigated.