"DNA-DNA Tetraplex Model of Paired Sense-Antisense RNA Synthesis".*

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,

^@ Present Addresses: Activator RNA Research, Physicians’ Educational Series, Atherton, CA  94027-5446
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.

Synthesis of paired sense-antisense RNA species is varied and ubiquitous within mammalian cells, such as the simultaneous sense-antisense RNA transcription of  genes Tsix and Xist during early mouse embryonic life (Xu N., Tsai C-L, and Lee J.T., Science, 311: 1149-1152, (2006). In other mammalian cells, the zone of pairing is small compared to the overall length of the paired RNA strands, with a resultant high degree of asymmetry within the RNA synthesis process. Such asymmetry permits close association between sense and antisense RNAs of widely different lengths, allowing coupling of disparate RNA functions to a common gene locus. We have studied the ultrastructure of chromosome-chromosome contact points by high-resolution electron microscopy during interphase in several types of mammalian cells which indicate DNA-DNA tetraplex structures favoring the synthesis of paired sense-antisense RNA molecules as in the mouse embryo. The contact points between adjacent interphase chromosomes consist of 20 nm caliber microcylinders formed from two 10 nm caliber euchromatin microfibrils from each of two adjacent chromosomes. Such close apposition of two chromosomal  structures allows a physical interaction between complementary DNA sequences from each chromosome, which favors a simultaneous transcription of paired sense-antisense RNA from such a DNA tetraplex. Simultaneous paired sense-antisense transcription usually occurs at one gene locus, and may be paired for part or all of the length of each RNA product. Because RNA-RNA duplexes are more stable than DNA-RNA or DNA-DNA duplexes, some of the paired sense-antisense products from one gene locus may appear as RNA-RNA duplexes, and be easily transported to adjacent cells as inducers during embryogenesis. A similar DNA-DNA tetraplex model of paired sense-antisense RNA synthesis has been proposed for the single-stranded integration of oncogenic viral DNA into mouse lymphoma DNA (Frenster JH, Biophys. J., 15: p. 137a (1975). A similar occurrence during chromosome-chromosome kissing is postulated.

Supported in part by USPHS Research Career Development Award CA-17857 from the National Cancer Institute.

Kissing Chromosomes Mediate Paired  Sense-Antisense RNA Transcription on a DNA-DNA Tetraplex.

1. Frenster JH, and Hovsepian JA, "Ultrastructure  of Closed Loops within Euchromatin of Isolated Lymphocyte Nuclei", Molec. Biol. Cell, vol. 15, suppl., p. 450a (November, 2004).

2. Kioussis D, "Gene regulation: Kissing Chromosomes",  Nature vol. 435, no. 7042, pp. 579-580 (June 2,  2005).

3. Frenster JH, and Hovsepian JA, "Ultrastructure of Euchromatin Contact Points between the Closed Loops of Adjacent Interphase Chromosomes", Molec. Biol. Cell, vol. 16, suppl., p. 1280a (December, 2005).

4. Tufarelli C, "The silence RNA keeps: cis mechanisms of RNA mediated epigenetic silencing in mammals"., Philosophical Transactions of The Royal Society B, Volume 361, Number 1465 / 29 January 2006, Pages: 67–79

5. Xu N., Tsai C-L, and Lee J.T., "Transient Homologous Chromosome Pairing Marks the Onset of X Inactivation",   Science, 311: 1149-1152, (February 24, 2006).

6. Frenster JH, and Hovsepian JA, "Kissing Chromosomes and Paired Sense-Antisense RNA Synthesis", Cold Spring Harbor Symposium on Quantitative Biology, vol. 71, page 62, May 31-June 5, 2006.

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