antisense RNA network, a new hypothesis

Fang Dexing dfang at PUBLIC1.PTT.JS.CN
Tue Nov 9 21:58:08 EST 1999


Antisense RNA Network:  Another Defense System of Animals

Fang Dexing
Huadong Research Institute for Medical Biotechnics
293 East Zhongshan Road
Nanjing 210002
P. R. China
E-mail:  fangdx at hotmail.com

ABSTRACT

    All kinds of RNAs within the animal body are antisense molecules
against their transcription template genome DNAs, they form a network,
antisense RNA network [2].  One of functions of the network is
recognizing and eliminating specifically the nucleic acids mutated
within the body and those invaded into the body from outside.  This
makes the antisense RNA network become another defense system of animals
like the known immune network.  The antisense RNA network is to nucleic
acids what the immune network is to proteins (antigens).

Key words:  antisense RNA, network, immune network, defense system

1.  INTRODUCTION

    Nucleic acids and proteins are two kinds of important macromolecules
within animal body.  Every individual has its own molecule composition,
and does not permit foreign macromolecules to invade and interfere with
the relative balance.  Against proteins (antigens), as we know, there is
immune network [1].  What plays role in defending DNAs and/or RNAs
(their invasion will be a greater danger than proteins')? The answer
would be antisense RNA network [2].  It is stated that there are many
kinds of antisense RNA and anti-antisense RNA fragments within animal
body, even in other kinds of life.  Because of self-modification or
other mechanisms, these RNAs base-pair, but do not hybridize with each
other.  The network participates in regulating the expression of certain
genes, and plays a pivotal role in specifically recognizing and
eliminating nucleic acids mutated within the body and those invaded into
the body from outside.  Antisense RNA network, together with the known
immune network, composes the whole defense systems of animal.

2.  DEFECTS OF IMMUNE NETWORK

    As we know, immune network advanced by Jerne [3] and modified by
others is composed of interacted immunoglobulins (antibodies and
anti-antibodies).  It plays an important role in eliminating mutant
cells within the body (immunologic surveillance) and rejecting foreign
microbes invaded into the body (anti-infection). But these activities
are restricted within narrow limits.  On the one hand, only after the
cells become tumor ones, can they be identified immunologically.  On the
other hand, when virulent microbes have infected the body, specific
antibodies can recognize and complex with them, but to destroy them
there must be help of other accessory factors, such as complements and
macrophages.  Even so, the infectious nucleic acids of the pathogen are
still dangerous.  Immune network acts only in protein level.

3.  FUNCTIONS OF ANTISENSE RNA NETWORK

    With differences to immunoglobulin interaction in immune network,
nucleic acid interaction is based on primary sequence, and molecules
composing antisense RNA network are all small RNAs.  Against any foreign
DNA or RNA, whatever its size and sequence are, there are antisense RNAs
in the antisense RNA network.  They recognize, hybridize with and then
destroy the targets by their catalytic activity (such as digestive
ribozyme) or with the help of other nonspecific factors.  Cells in
different parts of animal body are submitted to different mutation
events at all times.  Antisense RNAs act in the early stage of mutation,
thus much quicker in time to low the possibility of becoming tumor.
During  microbe (such as virus) infection, if pathogens have entered
cells and infectious nucleic acids released, antibodies can not work any
more, antisense RNAs are the only specific weapons for cleaning the
targets.

4.  EXPLANATIONS AND EVIDENCES FOR ANTISENSE RNA NETWORK

    Up to the present, there is almost no research report about natural
antisense RNAs against somatic mutation or microbial infection.  That is
not a surprise, because techniques are not enough now to measure and
analyze small RNAs in animal body in detail, which size is that of about
5s rRNA or less and which amount is very low.  Why are there such a low
amounts of antisense RNAs and how can they work?  There are two possible
explanations:  The first is that the antisense RNAs are expressed
constitutively in a low level.  Only when meeting the complementary
foreign DNA or RNA, is the corresponding clone induced and amplifies
rapidly.  After the antisense RNAs finish action, their amount returns
to normal level.  The second is that all antisense RNAs work like
enzymes (ribozymes), one molecules can act on many target molecules one
by one.  Thus the body does not need as large amounts of antisense RNAs
as those of antibodies produced after immunization.  An interesting
finding that might support these ideas comes from a paper by Bartel and
Szostak in Science [4].  They obtained ribozymes from a large pool of
random RNA molecules by a special selection protocol, rounds of
ligation, selection and amplification.  The antisense RNAs in antisense
RNA network seem to be just like Bartel-Szostak random RNA sequences,
special ones in the pool amplify in a similar way after the induction of
certain foreign nucleic acids.  It is certain that within the body the
amplification would be more complicated, but much more effectively.
However, the real mechanism is to be known.
    Even though no one has directly tested the internal antisense RNA
network, studies on synthetic antisense RNAs against cancers and
infectious microbes have been surprising.  As to antiviral infection,
the inhibition of antisense RNAs against virus has been demonstrated in
studies on human immunodeficiency virus [5], human hepatitis B virus
[6], herpes simplex virus [7], vesicular stomatitis virus [8],
adenovirus [9], influenza virus [10], Rous sarcoma virus [11], bovine
leukemia virus [12] and many other viruses.  It can be considered that
almost all viral infections could be prevented by antisense RNAs.

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