Biochemistry (Moscow) (v.78, #6)

Regulatory small RNAs by V. A. Gvozdev (561-561).
Recent years have been marked by a burst of studies on the role of various RNAs in the regulation of gene expression. These regulatory effects act on the level of both chromatin in the nuclei and the cytoplasm during translation. The review papers of this issue are mainly dedicated to different types of small RNAs of 20–30 nucleotides. The small RNAs control diverse cellular functions including genome protection against transpositions of mobile elements of the genome.
Keywords: microRNAs; siRNAs; piRNAs; heterochromatin; transposon

Successful heterochromatin formation is critical for genome stability in eukaryotes, both to maintain structures needed for mitosis and meiosis and to silence potentially harmful transposable elements. Conversely, inappropriate heterochromatin assembly can lead to inappropriate silencing and other deleterious effects. Hence targeting heterochromatin assembly to appropriate regions of the genome is of utmost importance. Here we focus on heterochromatin assembly in Drosophila melanogaster, the model organism in which variegation, or cell-to-cell variable gene expression resulting from heterochromatin formation, was first described. In particular, we review the potential role of transposable elements as genetic determinants of the chromatin state and examine how small RNA pathways may participate in the process of targeted heterochromatin formation.
Keywords: heterochromatin; genome stability; transposable elements

piRNA clusters as a main source of small RNAs in the animal germline by I. A. Olovnikov; A. I. Kalmykova (572-584).
PIWI subfamily Argonaute proteins and small RNAs bound to them (PIWI interacting RNA, piRNA) control mobilization of transposable elements (TE) in the animal germline. piRNAs are generated by distinct genomic regions termed piRNA clusters. piRNA clusters are often extensive loci enriched in damaged fragments of TEs. New TE integration into piRNA clusters causes production of TE-specific piRNAs and repression of cognate sequences. piRNAs are thought to be generated from long single-stranded precursors encoded by piRNA clusters. Special chromatin structures might be essential to distinguish these genomic loci as a source for piRNAs. In this review, we present recent findings on the structural organization of piRNA clusters and piRNA biogenesis in Drosophila and other organisms, which are important for understanding a key epigenetic mechanism that provides defense against TE expansion.
Keywords: piRNA; PIWI; transposable elements; germline; chromatin; Drosophila

Multifunctionality of PIWI proteins in control of germline stem cell fate by E. Y. Yakushev; O. A. Sokolova; V. A. Gvozdev; M. S. Klenov (585-591).
PIWI proteins interacting with specific type of small RNAs (piRNAs) repress transposable elements in animals. Besides, they have been shown to participate in various cellular processes: in the regulation of heterochromatin formation including telomere structures, in the control of translation and the cell cycle, and in DNA rearrangements. PIWI proteins were first identified by their roles in the self-renewal of germline stem cells. PIWI protein functions are not limited to gonadogenesis, but the role in determining the fate of stem cells is their specific feature conserved throughout the evolution of animals. Molecular mechanisms underlying these processes are far from being understood. This review focuses on the role of PIWI proteins in the control of maintenance and proliferation of germinal stem cells and its relation to the known function of PIWI in transposon repression.
Keywords: small RNA; RNA silencing; piRNA; heterochromatin; stem cells; PIWI

Over the past decade, PIWI-interacting RNAs (piRNAs) have emerged as the most intriguing class of small RNAs. Almost every aspect of piRNA biology defies established rules of the RNA interference world while the scope of piRNA functional potential spans from transcriptional gene silencing to genome defense to transgenerational epigenetic phenomena. This review will focus on the genomic origins, biogenesis, and function of piRNAs in the mouse testis — an exceptionally robust experimental system amenable to genetic, cell-biological, molecular, and biochemical studies. Aided and frequently guided by knowledge obtained in insect, worm, and fish germ cells, mouse spermatogenesis has emerged as the primary model in understanding the role of this conserved pathway in mammals.
Keywords: piRNA; PIWI; retrotransposon; germ cell; spermatogenesis; mouse; DNA methylation

The role of transcription in heterochromatin formation in the nuclei of eukaryotes, originally shown for the pericentromeric heterochromatin assembly in fission yeasts, has now become an accepted paradigm extended to multicellular eukaryotes. It has been shown that small RNAs involved in the RNA interference system in its broadest sense can play an important role in this multi-step process — they are recognized by complementary interactions with the newly formed nuclear transcripts and recruit protein complexes to the local genomic sites for heterochromatinization. The role of transcription as a trigger of this process at the sites of genomic repeats will be considered in this review using various examples of heterochromatin formation, with an emphasis on discussion of its role in trans-chromosomal interactions causing gene inactivation.
Keywords: heterochromatin; transcription; epigenetics; trans-inactivation; paramutation; variegated position effect

Quantitative aspects of RNA silencing in metazoans by A. M. Sergeeva; N. Pinzón Restrepo; H. Seitz (613-626).
Small regulatory RNAs (microRNAs, siRNAs, and piRNAs) exhibit several unique features that clearly distinguish them from other known gene regulators. Their genomic organization, mode of action, and proposed biological functions raise specific questions. In this review, we focus on the quantitative aspect of small regulatory RNA biology. The original nature of these small RNAs accelerated the development of novel detection techniques and improved statistical methods and promoted new concepts that may unexpectedly generalize to other gene regulators. Quantification of natural phenomena is at the core of scientific practice, and the unique challenges raised by small regulatory RNAs have prompted many creative innovations by the scientific community.
Keywords: small RNAs; RNA silencing; RNA interference

Biogenesis, evolution, and functions of plant microRNAs by P. P. Pashkovskiy; S. S. Ryazansky (627-637).
This review focuses on the biological role of one class of plant small RNAs, ∼22-nt microRNAs (miRNAs). The majority of plant miRNA targets are genes encoding the effector factors of cell signaling pathways. The regulation of their expression is necessary for both ontogenesis and rapid response of plants to biotic and abiotic stress factors. We also summarized current views on the biogenesis and evolution of plant miRNAs as well as the techniques used for their investigation.
Keywords: microRNA; stress; plant

New functions of small nucleolar RNAs by J. A. Makarova; S. M. Ivanova; A. G. Tonevitsky; A. I. Grigoriev (638-650).
Small nucleolar RNAs (snoRNAs) are one of the most abundant and well-studied groups of non-coding RNAs. snoRNAs are mostly engaged in processing of rRNA. However, recent data indicate that snoRNAs are also involved in other processes including regulation of alternative splicing, translation and oxidative stress. snoRNAs are also involved in pathogenesis of some hereditary diseases and cancer. Therefore, the range of snoRNAs’ functions is significantly wider than it has been assumed earlier.
Keywords: snoRNA; scaRNA; sdRNA; miRNA; noncoding RNA; RNA silencing; oncogenesis

Identification of proteins specifically interacting with YB-1 mRNA 3′ UTR and the effect of hnRNP Q on YB-1 mRNA translation by D. N. Lyabin; L. F. Nigmatullina; A. N. Doronin; I. A. Eliseeva; L. P. Ovchinnikov (651-659).
In this study, proteins specifically interacting with the 3′ untranslated region (UTR) of mRNA of the multifunctional Y-box-binding protein 1 (YB-1) were identified. One of these, hnRNP Q, was shown to specifically interact with the regulatory element (RE) in YB-1 mRNA 3′ UTR and to inhibit translation of this mRNA. Its binding to the RE was accompanied by displacement from this element of the poly(A)-binding protein (PABP), a positive regulator of YB-1 mRNA translation, and by enhanced binding of the negative YB-1 mRNA translation regulator — YB-1 itself.
Keywords: protein YB-1; protein hnRNP Q; translation regulation; 3′ untranslated region of mRNA

Understanding the relationship between the visual pigment rhodopsin and Zn2+ under normal conditions and in case of deficiency of the latter, as well as the realization of the role of Zn in the development of the hereditary disease retinitis pigmentosa, have great theoretical and practical importance. In this mini-review, we briefly examine the basic experimental data on the role of Zn2+ in the retina and photoreceptors, binding of endogenous Zn2+ by zinc-binding sites of differing affinities in rhodopsin, the influence of the exogenous Zn2+ on various properties of rhodopsin, including its ability for phosphorylation and activation of transducin, as well as its thermal stability and regeneration. Conflicting results on the correlation between Zn2+ content in the blood serum and the development of retinitis pigmentosa in patients are demonstrated. The review also shows the success of the application of animal models of induced or hereditary retinal degeneration and discusses some of the methodological approaches and therapeutic techniques to relieve the manifestations of this disease.
Keywords: retina; rhodopsin; Zn2+ ; retinitis pigmentosa; degeneration and apoptosis of photoreceptors

Fc fragments (hFc) of human myeloma IgG2 proteins LOM and SIN having core hinge (Cys-Cys-Val-Glu-Cys-Pro-Pro-Cys) were first obtained by a modified proteolytic procedure. The thermostability of CH2 domains inside of standard Fc, hFc fragments, and intact IgG2 LOM and SIN was studied by fluorescence spectroscopy. It was found that CH2 domains of intact IgG2 are destabilized. The destabilization is accompanied by reduced ability of IgG2 to inhibit the activation of complement system by classical pathway. This could be due to the decrease in the affinity of CH2 domains to factor C1q.
Keywords: immunoglobulin IgG2; Fc fragment; CH2 domain; complement system factor C1q; myeloma; stability

Extracellular phosphomannan as a phosphate reserve in the yeast Kuraishia capsulata by L. P. Lichko; T. V. Kulakovskaya; I. S. Kulaev (674-677).
We have found that extracellular phosphomannan is the main phosphate reserve in the yeast Kuraishia capsulata, in contrast to other yeast species effectively absorbing Pi. Under nitrogen starvation, K. capsulata absorbed essentially all Pi from the medium containing 240 mM glucose, 2.5 mM MgSO4, and 11 mM KH2PO4. Inorganic polyphosphate level in the cells was about 14% of the Pi absorbed. Most of the Pi (∼60%) was found in the fraction of extracellular phosphomannan that can be used as a carbon and phosphorus source by this yeast in deficient media.
Keywords: inorganic polyphosphate; phosphomannan; phosphate accumulation; nitrogen deficit; yeast; Kuraishia capsulata

Retraction to: “Signaling pathways in tumor vasculogenic mimicry” by Yvette W. J. Paulis; Patricia M. M. B. Soetekouw; Henk M. W. Verheul; Vivianne C. G. Tjan-Heijnen; Arjan W. Griffioen (678-678).