Abstract The phenomenon of the positive influence of introns on the expression of a corresponding gene, which is called intron-mediated enha
Abstract The phenomenon of the positive influence of introns on the expression of a corresponding gene, which is called intron-mediated enhancement (IME), is characteristic of a wide variety of organisms, including nematodes, insects, mammals, fungi, and plants, and occurs due to an as-yet-undefined fundamental mechanism. IME introns have been used for a long time, in particular, in plant biotechnology. Understanding the mechanisms of this phenomenon allows predicting and easily generating stimulatory introns with the given properties and creating highly advantageous phenotypes. It will also give the greenlight to the use of IME in gene therapy and to improve the production of pharmaceutical proteins. In this review, we analysed previously proposed models of IME functioning mechanisms and identified factors that can directly or indirectly determine IME under different conditions and at different levels of gene expression, such as experimental methods of IME research, regulatory RNAs, sequence properties, intron position and orientation, factors at the levels of DNA, transcription, splicing, mRNA, translation, genes in which IME is detected, tissue specificity, repression and how some factors relate to each other by importance. Since there is no single mechanism of IME, and the effect may differ in different species, when modelling this process, only the cases of IME affecting the same level of expression should be compared with each other, taking into account the experimental conditions. Identifying the biological factors that may determine IME and the relationship between them will help in the future to create a corresponding data set suitable for machine learning and try to solve the mystery of the IME phenomenon using machine learning.