"Chromosome-Chromosome Contact Points and Paired Sense-Antisense RNA Synthesis."

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

Departments of ¹ Radiology and ² Medicine, Stanford University School of Medicine, Stanford, California 94035, USA
^@ Present Addresses: RNA Research, Physicians' Educational Series, Atherton, CA 94027-5446, USA

Phone:  650/367-6483;   FAX:   650/364-1773,  e-mail:   frensasc@ix.netcom.com
Supported in part by a USPHS Research Career Development Award CA-17857 to J.H.F.

The study by Coudert AE, et al., Nucleic Acids Research, vol. 33, no. 16, pp. 5208-5218 (September 12, 2005), reveals the expression and regulation of the Msx1 natural antisense transcript during development of the mouse embryo. The Msx1 transcript antisense RNA was found to be 2184 nt long in the mouse, and to play a role in regulating cell differentiation and organ morphogenesis during embryogenesis. We have studied the ultrastructure of chromosome-chromosome contact points during interphase in mammalian cells, possibly indicating DNA-DNA tetraplex structures which favor 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 10 nm caliber euchromatin microfibrils from each of two adjacent chromosomes. Such close apposition of chromatin structures could allow 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.

Figure 1: Synthesis of Antisense RNA after formation of Chromosome-Chromosome contact points.

Active portions of chromosome A contact complementary portions of chromosome B, freeing the remaining strand of DNA for the paired synthesis of antisense RNA on chromosome B. The formation of a DNA-DNA tetraplex structure is postulated, based on interacting DNA-DNA loops.

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