No abstract

X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes ( SSR4 , REPS2 , and SEPT6 ), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants.

Mammalian mitochondrial ribosomes contain a set of modified nucleotides, which is distinct from that of the cytosolic ribosomes. Nucleotide m4C840 of the murine mitochondrial 12S rRNA is equivalent to the dimethylated m4Cm1402 residue of Escherichia coli 16S rRNA. Here we demonstrate that mouse METTL15 protein is responsible for the formation of m4C residue of the 12S rRNA. Inactivation of Mettl15 gene in murine cell line perturbs the composition of mitochondrial protein biosynthesis machinery. Identification of METTL15 interaction partners revealed that the likely substrate for this RNA methyltransferase is an assembly intermediate of the mitochondrial small ribosomal subunit containing an assembly factor RBFA.

RNA molecules of all species contain modified nucleotides and particularly m 5 U residues. The vertebrate mitochondrial small subunit rRNA contains m 5 U nucleotide in a unique site. In this work we found an enzyme, TRMT2B, responsible for the formation of this nucleotide and m 5 U residues in a number of mitochondrial tRNA species. Inactivation of the Trmt2B gene leads to a reduction of the activity of respiratory chain complexes I, III and IV, containing the subunits synthesized by the mitochondrial protein synthesis apparatus. Comparative sequence analysis of m 5 U-specific RNA methyltransferases revealed an unusual evolutionary pathway of TRMT2B formation which includes consecutive substrate specificity switches from the large subunit rRNA to tRNA and then to the small subunit rRNA.

Equilibria E 4000 Crystal Structure, Phase Relations and Electrochemical Properties of Monoclinic Li 2 MnSiO 4 . -Phase relations in the MnO-SiO 2 -Li 4 SiO 4 subsystem are characterized by powder XRD after solid state reactions in hydrogen at 950-1150°C. Li2MnSiO4, existing in the system, crystallizes in the monoclinic space group P21/n with Z = 4, and is isostructural with γII-Li2ZnSiO4 and low-temperature Li2MgSiO4. Only 4% Li can be extracted from Li2MnSiO4 in an electrochemical cell between 3.5 and 5 V against Li metal. Neither the orthorhombic nor the monoclinic modification of Li2MnSiO4 is suitable for battery applications. -(POLITAEV, V. V.; PETRENKO*, A. A.; NALBANDYAN, V. B.; MEDVEDEV, B. S.; SHVETSOVA, E. S.; J. Solid State Chem. 180 (2007) 3, 1045-1050; Fac. Chem., Rostov State Univ., Rostov-on-Don 344090, Russia; Eng.) -W. Pewestorf 52-016

No abstract

Post-translational modifications by ubiquitin-like proteins (UBLs) are essential for nearly all cellular processes. Ubiquitin-related modifier 1 (Urm1) is a unique UBL, which plays a key role in tRNA anticodon thiolation as a sulfur carrier protein (SCP) and is linked to the noncanonical E1 enzyme Uba4 (ubiquitin-like protein activator 4). While Urm1 has also been observed to conjugate to target proteins like other UBLs, the molecular mechanism of its attachment remains unknown. Here, we reconstitute the covalent attachment of thiocarboxylated Urm1 to various cellular target proteins in vitro, revealing that, unlike other known UBLs, this process is E2/E3-independent and requires oxidative stress. Furthermore, we present the crystal structures of the peroxiredoxin Ahp1 before and after the covalent attachment of Urm1. Surprisingly, we show that urmylation is accompanied by the transfer of sulfur to cysteine residues in the target proteins, also known as cysteine persulfidation. Our results illustrate the role of the Uba4-Urm1 system as a key evolutionary link between prokaryotic SCPs and the UBL modifications observed in modern eukaryotes.

Purpose. Turkic peoples started to spread in the Baraba forest-steppe in the 8th century AD, bringing in their material culture and mixing with local population. At present, there have been recorded two settlements: Lozhka-4 and Sadovka in the Baraba forest-steppe. More commonly studied burial complexes include Chulym-2, Bolshie Luki-1, -3, Vladimirovka-3, Tretie Otdelenie-1, -2, Bazovo-1, Bazovo-2, Vengerovo-1, Vengerovo VII, Preobrazhenka-3, Sopka-2, Turunovka-3A, Hodunekovo, Aul-Koshkul, Oltary-1, Osintsevo-IV. Burial grounds are represented in three types: single mounds, groups of mounds and ground burials. We described the content of the ground burial found in 2016, which belongs to the Early Middle Age and was situated on the settlement of the Krotovo culture Vengerovo-2. Results. It was a single ground burial, located in the South-East – North-West direction. The skeleton was placed in an elongated position, arms along the body, the skull turned to the left and tilted to the shoulder. There was an iron knife in a poor condition near the diseased man’s left hand. There were found two horn buckles to the left of the sacrum and to the right of the lumbar spine. According to the classification by V. I. Molodin of the bone buckles of the Baraba forest-steppe, the full buckle can be referred to the type I, subtype 2, and it can be dated to the 7–8th centuries. By analogy with the buckles of the Srostkinskaya culture, the buckle from Vengerovo-2 is rectangular with a rounded frame, has a T-shape, and the slot for rolling the tongue is separated from the end of the slot isthmus. Such products were widely spread in the Middle Age cultures of Siberia and are dated in a broad range to the 8–10th centuries. The closest analogues to these items can be found in materials of the site Tartas-1, where burials of different times and cultures are represented, and which is situated near Vengerovo-2 settlement. Similar ground burials had been found at the Tartas-1 cemetery in 2008, 2009 and 2011. By the traits of their burial rite and inventory, they were referred to the ancient Turkic culture. Tartas-1 is an elite cemetery of the Turkic epoch on the territory of the Baraba forest-steppe as the site contained stuffed horses and a wide set of accessories such as weapons, jewelry, art objects and horse harness in its burials. There is another similar site, Turunovka-3A, where three shallow-dug soil graves were uncovered at the edge of the high shore terrace. The ancient graves of the Baraba burial ground Vengerovo-2 also do not include ceramic vessels. Conclusion. On the basis of the specific features of the burial rite and inventory, the burial on the site Vengerovo-2 is referred to a common type which was left by the population of the ancient Turkic culture of the Baraba.