Search for characteristic structural features of mammalian mitochondrial tRNAs

a1 Unité Propre de Recherche 9002 du Centre National de la Recherche Scientifique, Département Mécanismes et Macromolécules de la Synthèse Protéique, et Cristallogenèse, Institut de Biologie Moléculaire et Cellulaire, F-67084 Strasbourg Cedex, France
a2 Institute of Theoretical Chemistry, A-1090 Vienna, Austria


A number of mitochondrial (mt) tRNAs have strong structural deviations from the classical tRNA cloverleaf secondary structure and from the conventional L-shaped tertiary structure. As a consequence, there is a general trend to consider all mitochondrial tRNAs as “bizarre” tRNAs. Here, a large sequence comparison of the 22 tRNA genes within 31 fully sequenced mammalian mt genomes has been performed to define the structural characteristics of this specific group of tRNAs. Vertical alignments define the degree of conservation/variability of primary sequences and secondary structures and search for potential tertiary interactions within each of the 22 families. Further horizontal alignments ascertain that, with the exception of serine-specific tRNAs, mammalian mt tRNAs do fold into cloverleaf structures with mostly classical features. However, deviations exist and concern large variations in size of the D- and T-loops. The predominant absence of the conserved nucleotides G18G19 and T54T55C56, respectively in these loops, suggests that classical tertiary interactions between both domains do not take place. Classification of the tRNA sequences according to their genomic origin (G-rich or G-poor DNA strand) highlight specific features such as richness/poorness in mismatches or G-T pairs in stems and extremely low G-content or C-content in the D- and T-loops. The resulting 22 “typical” mammalian mitochondrial sequences built up a phylogenetic basis for experimental structural and functional investigations. Moreover, they are expected to help in the evaluation of the possible impacts of those point mutations detected in human mitochondrial tRNA genes and correlated with pathologies.

(Received May 25 2000)
(Revised June 26 2000)
(Accepted July 10 2000)

Key Words: aminoacylation identity; bizarre tRNAs; compilation; G-U pairs; neurodegenerative disorders; T-loop.

c1 Reprint requests to: Catherine Florentz, Unité Propre de Recherche 9002 du Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 15, rue René Descartes, 67084 Strasbourg Cedex, France; e-mail: C.Florentz@ibmc.u-strasbg.fr.
p1 Present address: California Institute of Technology, Division of Biology, Pasadena, California 91125, USA.
p2 Present address: Institute for Structural Biology and Drug Discovery, Virginia Biotechnology Research Park, 800 East Leigh Street, Richmond, Virginia 23219, USA.