Published in: Proc. Natl. Acad. Sci., USA, vol. 55, no. 4, pp. 858-865 (April, 1966):

"An RNA-Histone Complex in Mammalian Cells: The Isolation and Characterization of a New RNA Species".

By William Benjamin, Orville A. Levander, Alfred Gellhorn, and Robert H. DeBellis

Department of Medicine, College of Physicians and Surgeons, Columbia University, and the Medical Service, Francis Delafield Hospital, New York


Many lines of evidence indicate that all specialized cells contain the total genetic information characteristic of the organism, but the mechanisms involved in the selective expression of this total information are unknown. Stedman and Stedman [1] suggested that the histones, the basic proteins of the nucleus, could serve as the controlling mechanism. Most cells of an organism, however, have the same histones [2, 3], and since the histones of individual organs such as liver or brain do not change appreciably during development [4] or during carcinogenesis [5, 6], it seems unlikely that the histones alone possess sufficient specificity for the control of gene function.

Sypherd and Strauss [7] suggested that an associated RNA species complementary to particular sequences of DNA could provide a mechanism for the histones to act as repressors by conferring additional specificity to these proteins. Huang and Bonner [8] have recently described an RNA-histone complex in the pea seedling. We have concurrently carried out experiments on the nucleoprotein fraction isolated from normal rat liver and have found an RNA species with a high adenine and uridine content which is intimately associated with the nucleoprotein fraction and is resistant to ribonuclease. After extraction from the basic protein with phenol and detergent, this RNA species is RNase-sensitive and is heterogenous by sucrose density gradient analysis.

Materials and Methods:

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Discussion:

The biological role of the histone-bound RNA described in the present report is unknown. It is possible that this trace component is an intermediate in the synthesis of messenger RNA. As messenger RNA is transcribed off the DNA template, it may be bound to nuclear basic protein prior to its attachment to the ribosome.

Another possibility is that the histone-bound RNA may play a primary role in the control of gene function. Sypherd and Strauss [7] postulated the existence of a hypothetical repressor substance containing both protein and polyribonucleotide moieties. The protein portion of the molecule was presumed to have specificity for small effector substances, whereas the RNA component was thought to have base-pairing specificity for the DNA of the gene.

Paigen [19] suggested a system of gene regulation based on the concept that any given RNA is transcribed along only one strand (up strand) of DNA and that the function of the unread strand (down strand) of DNA is to displace the RNA product from the DNA by competitive hydrogen bonding. If the RNA of the histone complex were transcribed from a regulator of the genome and had areas complementary to some portion of the down strand of the structural gene, the complex could act as a repressor of genetic information by base pairing with the unread strand of DNA, preventing messenger RNA synthesis. However, the regulator RNA of the histone complex could also control gene action by a different mechanism. Native DNA is believed to exist as a coiled helix complexed with histone [20, 21]. If the regulator