John H. Frenster ^{1, @} and Jeannette A. Hovsepian ^{2, @}

Departments of ¹ Medicine and of ² Radiology, Stanford University School of Medicine, Stanford, California  94305, USA,

^@ Present Addresses: Physicians’ Educational Series, Atherton, CA  94027-5446 USA.
Phone:  +1 650 367 6483;   Fax:  +1 650 364 1773;   e-mail:   frenster@euchromatin.net

* Supported in part by a USPHS Research Career Development Award (CA-17857) from the National Cancer Institute to J.H.F.

Abstract:

The rate of cellular RNA synthesis declines during the mitotic stages of cell division (1) and during cell differentiation (2) in mammals. High-resolution ultrastructural probes of DNase I-sensitive sites within human intact bone-marrow cells reveal a progressive decrease in the number of active DNA probe sites per cell through the early and late stages of mitotic prophase, to an absence of any probe sites in metaphase, anaphase and early telophase, with a subsequent rapid temporary increase in the number of probe sites per cell in late telophase, later returning to a basal level in interphase. Recent studies reveal the role of small RNA species in activating the initiation of DNA transcription within repressed chromatin (3), and in mediating the re-programming of already-active mammalian chromatin by yeast RNA species (4). Small RNA species are found to shuttle from the nucleus to the cytoplasm during cell mitosis, and to return to the cell nuclei of the daughter cells after mitosis is completed in interphase (5). The observed overshoot in the number of active DNA sites in late telophase suggests that normal re-programming of the daughter cells after mitosis (6) includes a temporary phase in which extra DNA sites are opened, only to be closed subsequently in the basal state of cell interphase. Such a temporary overshoot of re-programming could reflect active sites which have a role in the recovery phase of normal mitotic re-programming, but not during subsequent interphase.

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

References:

1. Nakatsu SL, Masek MA, Landrum S, and Frenster JH, "Activity of DNA Templates During Cell Division and Cell Differentiation", Nature vol. 248, no. 5446, pp.  334-335 (March 22, 1974).

2. Frenster JH, Nakatsu SL, and Masek MA, "Ultrastructural Probes of DNA Templates within Human Bone Marrow and Lymph Node Cells", Adv. Cell. Molec. Biol. 3: 1-19 (1974), ed. DuPraw EJ, New York: Academic Press.

3. Frenster JH, "Nuclear RNA Species Activate DNA Transcription Within Chromatin", FASEB Journal 13: No. 7, A1506 (April 23, 1999).

4. Frenster JH, "Yeast RNA Re-Programming of Already-Active Mammalian Chromatin", "RNA 2002", p. 592, Bethesda, MD: The RNA Society, May 28th - June 2nd, 2002.

5a. Goldstein L, “Stable Nuclear RNA Returns to Post-Division Nuclei Following Release to Cytoplasm during Mitosis”, Exp. Cell Res. vol. 89,  no. 2, pp. 421-425 (December, 1974).

5b. Goldstein L, Wise GE, and Ko C, "Small Nuclear RNA Localization: An Electron Microscope Study", J. Cell Biol. vol. 73, no. 2, pp. 322-331 (May, 1977).

6.  Prasanth KV, Sacco-Bubulya PA, Prasanth SG, and Spector DL, “Sequential Entry of Components of Gene Expression Machinery into Daughter Nuclei”, Mol. Biol. Cell, vol. 14, no. 3, pp. 1043-1057 (March, 2003).

Additional References:

1. Hovsepian JA, and Frenster JH, "RNA-Induced Melting of DNA during Selective Gene Transcription", Mol. Biol. Cell, vol. 13, supp. p. 239a (November, 2002).

2. Saha S, Ansari AZ, Jarell KA, and Ptashne M, "RNA Sequences that Work as Transcriptional Activating Regions", Nucleic Acid Research, vol. 31, no. 5, pp. 1565-1570 (March 1, 2003).

3. Frenster JH,  "Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".