The Functions of N6-Methyladenosine in Nuclear RNAs.

N6-methyladenosine (m6A) is one of the most common modifications in both eukaryotic and prokaryotic mRNAs. It has been experimentally confirmed that m6A methylation is involved in the regulation of stability and translation of various mRNAs. Until recently, the majority of m6A-related studies have been focused on the cytoplasmic functions of this modification. Here, we review new data on the role of m6A in several key biological processes taking place in the cell nucleus, such as transcription, chromatin organization, splicing, nuclear-cytoplasmic transport, and R-loop metabolism. Based on analysis of these data, we suggest that m6A methylation of nuclear RNAs is another level of gene expression regulation which, together with DNA methylation and histone modifications, controls chromatin structure and functioning in various biological contexts.

Morphomechanical reactions and mechanically stressed structures in amphibian embryos, as related to gastrulation and axial organs formation.

Reactions of embryonic tissues to a distributed and concentrated stretching are described and compared with the mechanics of the normal gastrulation movements. A role of mechanically stressed dynamic cell structures in the gastrulation, demarcation of notochord borders and in providing proportionality of the axial rudiments is demonstrated. A morphomechanical scheme of amphibian gastrulation is presented.

Professor Lev Beloussov and the birth of morphomechanics.

The first explanations of the mechanisms of development of living organisms were proposed in antiquity. At that time two competing ideas existed, about the strict determination of embryonic structures (we call it the "Hippocrates line") and about the possible formation of structures from the unstructured condition ("Aristotle line"). We can trace the opposition between the "Hippocrates line" and "Aristotle line" from antiquity till the present time. At the end of the XIX century, experimental investigation of the mechanisms of integrity of development had started. In the XX century, the "Aristotle line" finds its expression in the Morphogenetic Field Theory of A.G. Gurwitsch, according to which cells of the organism are integrated in an organic whole. Since the 1970s, mechanical forces and tensions have been considered as integral factors of ontogenesis. One of the most productive scientific teams which worked in this area was the laboratory of Professor L.V. Beloussov from the Lomonossov Moscow State University, Russia. In the 1970s, Lev Beloussov and his colleagues discovered the presence of "passive" and "active" (i.e. metabolically-dependent) mechanical stresses in the tissues of developing organisms, their organization and stage-specific patterns. In 1980-1990 s, a lot of experimental data about the role of the patterns of mechanical stresses in morphogenesis and cell differentiation was accumulated. Based on the experimental data, Professor Beloussov and his colleagues developed a theory of the regulation of the development of living organisms on the basis of the interaction of passive and active mechanical stresses (Belousov-Mittenthal Theory), which forms the basis of a new science - morphomechanics.

Gastrulation in amphibian embryos, regarded as a succession of biomechanical feedback events.

Gastrulation in amphibian embryos is a composition of several differently located morphogenetic movements which are perfectly coordinated with each other both in space and time. We hypothesize that this coordination is mediated by biomechanical interactions between different parts of a gastrulating embryo based upon the tendency of each part to hyper-restore the value of its mechanical stress. The entire process of gastrulation in amphibian embryos is considered as a chain of these mutually coupled reactions, which are largely dependent upon the geometry of a given embryo part. We divide gastrulation into several partly overlapped steps, give a theoretical interpretation for each of them, formulate the experiments for testing our interpretation and describe the experimental results which confirm our point of view. Among the predicted experimental results are: inhibition of radial cell intercalation by relaxation of tensile stresses at the blastula stage; inversion of convergent intercalation movements by relaxation of circumferential stresses at the early gastrula stage; stress-promoted reorientation of axial rudiments, and others. We also show that gastrulation is going on under a more or less constant average value of tensile stresses which may play a role as rate-limiting factors. A macro-morphological biomechanical approach developed in this paper is regarded as complementary to exploring the molecular machinery of gastrulation.