Thermodynamic and structural consensus principle categorizes conserved interspecies miRNA subgroups, helps to predict mature miRNA location and structure, and points out new possible mechanisms of miRNA maturization

Although conservation of thermodynamics is much less studied than of sequences and structures, thermodynamic details are biophysical features different from but as important as structural features. As a succession of previous research which revealed the important relationships between thermodynamic features and miRNA maturization, this article applies interspecies conservation of miRNA thermodynamics and structures to study miRNA maturization. According to a thermodynamic and structural consensus principle, miRBase is categorized by conservation subgroups, which imply various functions. These subgroups are divided without the introduction of functional information. This suggests the consistency between the two processes of miRNA maturization and functioning. Different from prevailing methods which predict extended miRNA precursors, a learning-based algorithm is proposed to predict ~22bp mature parts of 2780 test miRNA genes in 44 species with a rate of 79.4%. This is the first attempt of a general interspecies prediction of mature miRNAs. Suboptimal structures that most fit the consensus thermodynamic and structural profiles are chosen to improve structure prediction. Distribution of miRNA locations on corresponding pri-miRNA stem-loop structures is then studied. Existing research on Drosha cleavage site is not generally true across species. Instead, the distance between mature miRNA and center loop normalized by stem length is a more conserved structural feature in animals, and the normalized distance between mature miRNA and ss-RNA tail is the counterpart in plants. This suggests two possibly-updating mechanisms of miRNA maturization in animals and plants. All in all, conservations of thermodynamics together with other features are shown closely related to miRNA maturization. Introduction MicroRNAs (miRNAs) are endogenous RNAs that play important regulatory roles by targeting mRNAs for cleavage or translational repression. Being non-coding genes, miRNAs is a big class of gene regulatory molecules which influence the output of many protein-coding genes [Bartel, 2004]. It is widely acknowledged that miRNA exists in multicellular organisms, including mammals, fish, worms, flies, cress, rice, etc. [Pasquinelli et al., 2000; Lagos-Quintana et al., 2001, 2002, 2003; Mourelatos et al., 2002; Ambros et al., 2003; Aravin et al., 2003; Dostie et al., 2003; Houbaviy et al., 2003; Kim et al., 2004; Lim et al., 2003a, 2003b; Michael et al., 2003; Park et al., 2002; Reinhart et al., 2002; Palatnik et al., 2003]. Although its existence in