, 48: 581–584, 1999
1521-6543/99 $12.00 + .00
Hypothetical Double-Helical Poly(A) Formation in a Cell
and Its Possible Biological Signicance
Margarita I. Zarudnaya and Dmytro M. Hovorun
Molecular Biophysics Department, Institute of Molecular Biology and Genetics,
Ukrainian National Academy of Sciences, 150, vul. Zabolotnoho, Kyiv, 252143, Ukraine
Arguments are presented in favor of capability of poly(A)-tracts
of cellular RNA to form double helices in vivo. It is suggested that
formation of the double helix in the mRNA poly(A) tail provides the
basis for such processes as polyadenylation termination, PAB I syn-
thesis autoregulation, and stabilization of ARE-containing mRNA
by ELAV-like proteins.
Life, 48: 581–584, 1999
Keywords Autoregulation of PAB I synthesis; ELAV-like proteins;
initiation of translation; polyadenylation termination;
poly(A) forms; poly(A) tail; stabilization of ARE-
Poly(A) tails of mRNA participate in many biological pro-
cesses, but in most cases the mechanisms of their functioning
are unknown (1). Depending on the physico-chemical condi-
tions, polyadenylic acid can exist in several forms, including
double-helical conformations (2). Can the double-helical forms
of poly(A) exist in a cell and participate in biological processes?
This question is discussed in this article.
POSSIBILITY OF FORMING POLY(A) DOUBLE-HELICAL
FORMS IN A LIVING CELL
The formation of poly(A) double helices is induced by pro-
tonation of adenine residues at the N1 position. Three different
double-helical forms and a “frozen” form arise. The “frozen”
form is a bulky structure consisting of single strands and ran-
domly distributed short double-stranded regions (3).
Depending on experimental conditions, poly(A) transition
from the single-stranded helix into the double-stranded state
Received 20 August 1999; accepted 7 October 1999.
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occurs at different pH values. For example, at room temperature
it occurs at pH
6.0 (0.15 M KCl) and pH
6.8 (0.001 M
KCl) (4). In partially methylated poly(A) (at the N1 position of
adenine) this transition takes place at pH 9.1 (0.15 M NaCl) at
room temperature (5).
Can double-helical forms of poly(A) be formed in a cell?
A priori it is impossible to rule out such a possibility, because
the local conditions in the appropriate cell microcompartments,
where RNA is located, are not known. A strong argument for
the existence of these forms is based on the fact that the nec-
essary conditions for RNA oligo(A)-tracts protonation can be
created by proteins interacting with RNA. In particular, the pro-
tonation of adenine residues can be induced by proton trans-
fer from acidic amino acid residues of proteins. Such transfer
has been registered in several model experiments with low-
molecular-mass compounds (6–8). Moreover, the protonation
of RNA adenosines and cytosines has been observed by Raman
spectroscopy inside tymoviral virions (9). It was proposed that
such protonation may result from direct interaction between the
RNA bases and acidic amino acids of the coat protein (10).
The poly(A) tails of mRNA speci cally interact with various
proteins and protein complexes (11–16), and these proteins can
be proton donors for the adenine residues. Thus the formation
of double oligo(A) helices in cellular RNAs is quite possible.
How might the double helix in mRNA poly(A) tail be formed,
if the strands in the double-helical poly(A) have parallel polar-
ity (17)? Taking into consideration the highly effective “frozen”
poly(A) formation (18), we suggested (19) that upon protona-
tion, poly(A) can form double helices not only with adjacent
molecules but also inside itself (intramolecular double helix).
Under the process of heat motion, a region inside a poly(A)
macromolecule or a poly(A) region in a RNA may take the
con guration with its segments being parallel-orientated as de-
picted, for example, in Fig. 1A–C. In protonation of the ade-
nine residues, these segments form the double helix (Fig. 1D).
We think (19) that the participation of the same poly(A)
macromolecule in the formation of both intramolecular and