Thermodynamic and structural consensus principle predicts mature miRNA location and structure, categorizes conserved interspecies miRNA subgroups, and hints new possible mechanisms of miRNA maturization

TL;DR

This study demonstrates that thermodynamic and structural conservation principles can predict mature miRNA locations across species, categorize conserved subgroups, and suggest new mechanisms of miRNA maturation, advancing understanding beyond sequence analysis.

Contribution

It introduces a novel interspecies prediction method for mature miRNAs based on thermodynamic and structural conservation, and proposes updated mechanisms of miRNA maturation in animals and plants.

Findings

Achieved 79.4% accuracy in predicting mature miRNA regions across 44 species.

Identified conserved structural features related to miRNA maturation sites.

Proposed new mechanisms of miRNA maturation based on normalized distances in structures.

Abstract

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.