John H. Frenster, Physicians’ Educational Series, Atherton, CA 94027-5446
Abstract:
Nuclear RNA species function as initiators of discontinuous DNA synthesis during gene replication (Cell 12, 483 (1977), and may also function as activators of pre-messenger RNA synthesis during gene transcription in chromatin (Nature 206, 680 (1965). DNase I-sensitive sites are confined to the euchromatin portion of the cell nucleus (Cancer Res. 31, 1128 (1971), and correlate with cell differentiation within human bone marrow cells (Nature 248, 334 (1974). Euchromatin and heterochromatin fractions can each be isolated from the same lymphocytes (Proc. Natl. Acad. Sci. U.S. 50, 1026 (1963), and can be used to assay RNA species as activators of DNA transcription within chromatin. Total nuclear RNA has significant activator effect on repressed heterochromatin, but little additional effect on already-active euchromatin. Total cytoplasmic RNA and total yeast RNA have intermediate levels of activity. Nuclear translation products (Proc. Natl. Acad. Sci. U.S. 46, 432 (1960) also have significant activity, but always less than total nuclear RNA, while nuclear ribonucleoprotein particles are still less active. Some nuclear RNA species are double-stranded and partially- resistant to RNase. Histones are uniformly inhibitory to already-active euchromatin. Nuclear RNA species offer the potential for high gene specificity during activation.
Supported in part by USPHS Research Grant CA-10174 from the National Cancer Institute.
1. "Nuclear Polyanions as De-Repressors of Synthesis of Ribonucleic Acid".
2. "Mechanisms of Repression and De-Repression within Interphase Chromatin".
3. "Mated Models of Gene Regulation in Eukaryotes".
4. "Selective Gene De-Repression by De-repressor RNA".
5. "Oncogenes as Molecular Targets within Active Chromatin".
6. "A Steroid Receptor Coactivator, SRA, Functions as an RNA and is Present in an SRC-1 Complex".