Small nucleolar RNA

The review considers small nucleolar RNAs (snoRNAs), an abundant group of non-protein-coding RNAs. In association with proteins, snoRNAs determine the two most common nucleotide modifications in rRNA and some other cell RNAs: 2′-O-methylation of ribose and pseudouridylation. In addition, snoRNAs are involved in pre-mRNA cleavage and the telomerase function. Almost all snoRNAs fall into two families, C/D and H/ACA, distinguished by conserved sequence boxes. Although the proteins of C/D and H/ACA snoRNPs have homologous regions, these snoRNPs are assembled differently. The RNA components of RNases P and MRP are also classed with snoRNAs. Another problem considered is the structure and function of small RNAs from Cajal bodies (small organelles associated with the nucleoli), which are similar to snoRNAs.     

Small nucleolar RNAs

Small nucleolar RNAs (snoRNAs) are an abundant class of non-protein-coding RNAs. In association with proteins they perform two most frequent nucleotide modifications in rRNAs and some other cellular RNAs: 2'-O-ribose methylation and pseudouridylation. SnoRNAs also participate in pre-rRNA cleavage and telomerase functions. Most snoRNAs fall into two families, box C/D and H/ACA, distinguished by the presence of conserved sequence boxes. Although C/D and H/ACA snoRNP proteins contain homologous regions, the assembly of these RNPs significantly differ. In addition, snoRNAs include the RNA component of RNAses P and MRP. The structure and function of small RNPs from Cajal bodies (small organelles associated with nucleoli) similar to snoRNP are also discussed.     

The lysophosphatidic acid 2 receptor mediates down-regulation of Siva-1 to promote cell survival

Lysophosphatidic acid (LPA) promotes cell survival through the activation of G protein-coupled LPA receptors. However, whether different LPA receptors activate distinct anti-apoptotic signaling pathways is not yet clear. Here we report a novel mechanism by which the LPA(2) receptor targets the proapoptotic Siva-1 protein for LPA-dependent degradation, thereby attenuating Siva-1 function in DNA damage response. The carboxyl-terminal tail of the LPA(2) receptor, but not LPA(1) or LPA(3) receptor, specifically associates with the carboxyl cysteine-rich domain of Siva-1. Prolonged LPA stimulation promotes the association of Siva-1 with the LPA(2) receptor and targets both proteins for ubiquitination and degradation. As a result, adriamycin-induced Siva-1 protein stabilization is attenuated by LPA in an LPA(2)-dependent manner, and the function of Siva-1 in promoting DNA damage-induced apoptosis is inhibited by LPA pretreatment. Consistent with this result, inhibition of the LPA(2) receptor expression increases Siva-1 protein levels and augments adriamycin-induced caspase-3 cleavage and apoptosis. Together, these findings reveal a critical and specific role for the LPA(2) receptor through which LPA directly inactivates a critical component of the death machinery to promote cell survival.     

Small nucleolar RNA genes

Small nucleolar RNAs (snoRNAs) are one of the most numerous and well-studied groups of non-protein-coding RNAs. In complex with proteins, snoRNAs perform the two most common nucleotide modifications in rRNA: 2′-OH-methylation of ribose and pseudouridylation. Although the modification mechanisms and snoRNP structures are highly conserved, the snoRNA genes are surprisingly diverse in organization. In addition to genes transcribed independently, there are genes that are in introns of other genes, form clusters transcribed from a common promoter, or clusters in introns. Interestingly, one type of gene organization usually prevails in different taxa. Vertebrate snoRNAs mostly originate from introns of protein-coding genes; a small group of snoRNAs are encoded by introns of genes for noncoding RNAs.     

Duodenase activates rat peritoneal mast cells via protease-activated receptors of type 1

It was found that duodenase, a serine protease from the bovine duodenum, activates rat peritoneal mast cells (PMC) in vitro presumably via protease-activated receptors (PARs). Like thrombin (a serine protease from the blood coagulation system) and the PAR1 agonist peptide (PAR1-AP), duodenase was shown to accelerate the secretion of β-hexosaminidase (a marker of cell degranulation) by PMC in a dose-dependent manner. The blockage of the proteolytic activity of duodenase toward the substrate Tos-Gly-Pro-Lys-pNA by the soybean Bauman-Birk protease inhibitor substantially reduced (by 40%) the ability of duodenase to stimulate the secretory activity of PMC. Pretreatment of PMC with duodenase decreased the β-hexosaminidase secretion induced by thrombin and PAR1-AP by 35 and 41.7 %, respectively, and abolished the antiinflammatory effect of activated protein C. At the same time, pretreatment of PMC with duodenase did not affect the secretion of β-hexosaminidase induced by compound 48/80, a nonspecific degranulator of mast cells. Duodenase, unlike PAR1-AP (30–100 μM), in a broad concentration range (10–100 nM) did not induce aggregation of human platelets, but suppressed the platelet aggregation elicited by PAR1-AP.     

Oncogenic comparison of human papillomavirus type 58 E7 variants

Human papillomavirus 58 (HPV58) ranks the second or third in East Asian cervical cancers. Current studies on HPV58 are scarce and focus on the prototype. Previously, we identified the three most common circulating HPV58 E7 strains contained amino acid alterations: G41R/G63D (51%), T20I/G63S (22%) and T74A/D76E (14%) respectively. Among them, the T20I/G63S variant (V1) had a stronger epidemiological association with cervical cancer. We therefore suggested that V1 possessed stronger oncogenicity than the other two variants. Here, we performed phenotypic assays to characterize and compare their oncogenicities with HPV58 E7 prototype. Our results showed that overexpression of V1 conferred a higher colony‐forming ability to primary murine epithelial cells than prototype (P < 0.05) and other variants, implicating its higher immortalising potential. Further experiments showed that both V1 and prototype enhanced the anchorage‐independent growth of NIH/3T3 cells (P < 0.001), implicating their stronger transforming power than the two other variants. Moreover, they possessed an increased ability to degrade pRb (P < 0.001), which is a major effector pathway of E7‐driven oncogenesis. Our work represents the first study to compare the oncogenicities of HPV58 E7 prototype and variants. These findings deepened our understanding of HPV58 and might inform clinical screening and follow‐up strategy.     

Dark matter in archaeal genomes: a rich source of novel mobile elements,defense systems and secretory complexes

Microbial genomes encompass a sizable fraction of poorly characterized, narrowly spread fast-evolving genes. Using sensitive methods for sequences comparison and protein structure prediction, we performed a detailed comparative analysis of clusters of such genes, which we denote “dark matter islands”, in archaeal genomes. The dark matter islands comprise up to 20 % of archaeal genomes and show remarkable heterogeneity and diversity. Nevertheless, three classes of entities are common in these genomic loci: (a) integrated viral genomes and other mobile elements; (b) defense systems, and (c) secretory and other membrane-associated systems. The dark matter islands in the genome of thermophiles and mesophiles show similar general trends of gene content, but thermophiles are substantially enriched in predicted membrane proteins whereas mesophiles have a greater proportion of recognizable mobile elements. Based on this analysis, we predict the existence of several novel groups of viruses and mobile elements, previously unnoticed variants of CRISPR-Cas immune systems, and new secretory systems that might be involved in stress response, intermicrobial conflicts and biogenesis of novel, uncharacterized membrane structures.