John H. Frenster,

Physicians’ Educational Series, Atherton, CA 94027-5446, USA.
E-mail:  frenster@euchromatin.net
WebSite:  http://www.euchromatin.net/current1.html

Nuclear RNA species function as initiators of DNA synthesis during DNA replication (Cell 12: 483 (1977), as activators of RNA synthesis during gene transcription within repressed chromatin (Nature 206: 680 (1965), and as a steroid receptor co-activator of transcription during steroid hormone stimulation of target cells (Cell 97: 17 (1999). Isolated RNA species have also been used for intra-marrow therapy of human leukemia (Nature 197: 1077 (1963). Repressed and active chromatin fractions were each isolated from the same lymphocytes (Proc. Natl. Acad. Sci. U.S. 50: 1026 (1963), and were then used to assay a wide variety of RNA species as activators of DNA transcription within repressed 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 gene activation.

Supported in part by USPHS Research Grants from the National Cancer Institute.

0. Frenster JH, "Ultrastructural Continuity Between Active and Repressed Chromatin", Nature vol. 205, no. 4978, pp. 1341-1342 (March 27, 1965).

1. Tseng BY, and Goulian M, "Initiator RNA of Discontinuous DNA Synthesis in Human Lymphocytes", Cell 12: 483 (1977).

2. Frenster JH, "Nuclear Polyanions as De-Repressors of Synthesis of Ribonucleic Acid", Nature 206: 680 (1965).

3. Lanz, RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, Tsai MJ, amd O'Malley BW, "A Steroid Receptor Coactivator, SRA, Functions as an RNA and is Present in a SRC-1 Complex",  Cell 97: 17 (1999).

4. De Carvalho S, "Effect of RNA from Normal Human Marrow on Leukaemic Marrow In-Vivo", Nature 197: 1077 (1963).

5. Frenster JH, Allfrey VG, and Mirsky AE, "Repressed and Active Chromatin Isolated from Interphsae Lymphocytes", Proc. Natl. Acad. Sci., USA 50: 1026 (1963).

6. Frenster JH, Allfrey VG, and Mirsky AE, "Metabolism and Morphology of Ribonucleoprotein Particles from the Cell Nucleus of Lymphocytes", Proc. Natl. Acad. Sci., USA 46: 432 (1960).

7. Mishra MC, Niu MC, and Tatum EL, "Induction by RNA of Inositol Independence in Neurospora crassa".
Proc. Natl. Acad. Sci. USA 72: 642 (1975).

8. Dobrzelewski J, Mileska Z, and Panusz H, "Effect on Transcription of Low-Molecular-Weight RNA from Calf Thymus Chromatin", Acta Biochim. Pol. 27:  75 (1980).

9. Review: "Selective Gene De-Repression by De-Repressor RNA," in: "Eukaryotic Gene Regulation", Volume 1, pp. 131-143, 1980, edit. Kolodny GM, CRC Press, Boca Raton, FL, USA.

10. Frenster JH, "Oncogenes as Molecular Targets within Active Chromatin", Clin. Cancer Res. 5: suppl. 1, 3855a (1999).

11. Huttenhofer A, Kiefmann M, Meier-Ewert S, O'Brien J, Lehrach H, Bachellerie J-P, and Brosius J, "RNomics: An Experimental Approach that Identifies 201 Candidates for Novel, Small, Non-Messenger RNAs in Mouse", EMBO J. 20: 2943 (2001).

12. Geiss G, Jin E, Guo J, Bumgarner R, Katze MG, and Sen GC, "A Comprehensive View of Regulation of Gene Expression by Double-Stranded RNA-Mediated Cell Signaling", J. Biol. Chem. 276: 30178 (2001).