The DEAD-box ATPase Dbp10/DDX54 initiates peptidyl transferase center formation during 60S ribosome biogenesis.

DEAD-box ATPases play crucial roles in guiding rRNA restructuring events during the biogenesis of large (60S) ribosomal subunits, but their precise molecular functions are currently unknown. In this study, we present cryo-EM reconstructions of nucleolar pre-60S intermediates that reveal an unexpected, alternate secondary structure within the nascent peptidyl-transferase-center (PTC). Our analysis of three sequential nucleolar pre-60S intermediates reveals that the DEAD-box ATPase Dbp10/DDX54 remodels this alternate base pairing and enables the formation of the rRNA junction that anchors the mature form of the universally conserved PTC A-loop. Post-catalysis, Dbp10 captures rRNA helix H61, initiating the concerted exchange of biogenesis factors during late nucleolar 60S maturation. Our findings show that Dbp10 activity is essential for the formation of the ribosome active site and reveal how this function is integrated with subsequent assembly steps to drive the biogenesis of the large ribosomal subunit.

An integrative platform for detection of RNA 2'-O-methylation reveals its broad distribution on mRNA.

Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain underexplored. We have developed NJU-seq, a sensitive method for unbiased 2'-O-methylation (Nm) profiling, and Nm-VAQ, a site-specific quantification tool. Using these tools in tandem, we identified thousands of Nm sites on mRNAs of human and mouse cell lines, of which 68 of 84 selected sites were further validated to be more than 1% 2'-O-methylated. Unlike rRNA, most mRNA Nm sites were from 1% to 30% methylated. In addition, mRNA Nm was dynamic, changing according to the circumstance. Furthermore, we show that fibrillarin is involved as a methyltransferase. By mimicking the detected Nm sites and the context sequence, the RNA fragments could be 2'-O-methylated and demonstrated higher stability but lower translation efficiency. Last, profiling of Nm sites in lung surgery samples revealed common signatures of lung cancer pathogenesis, providing potential new diagnostic markers.

Combinatorial and frequency properties of the ribosome ancestors.

BACKGROUND: The current ribosome has evolved from the primitive stages of life on Earth. Its function is to build proteins and on the basis of this role, we are looking for a universal common ancestor to the ribosome which could: i) present optimal combinatorial properties, and ii) have left vestiges in the current molecules composing the ribosome (rRNA or r-proteins) or helping in its construction and functioning. METHODS: Genomic public databases are used for finding the nucleotide sequences of rRNAs and mRNA of r-proteins and statistical calculations are performed on the occurrence in these genes of some pentamers belonging to the RNA proposed as optimal ribosome ancestor. RESULTS: After having exhibited a possible solution to the problem of an RNA capable of catalyzing peptide genesis, traces of this RNA are found in many rRNAs and mRNA of r-proteins, as well as in factors contributing to the construction of the current ribosome. CONCLUSIONS: The existence of an optimal primordial RNA whose function is to facilitate the creation of peptide bonds between amino acids may have contributed to accelerate the emergence of the first vital processes. Its traces should be found in many living species inside structures structurally and functionally close to the ribosome, which is already the case in the species studied in this article.

Comparative Mitogenome Analyses of Fifteen Ramshorn Snails and Insights into the Phylogeny of Planorbidae (Gastropoda: Hygrophila).

Ramshorn snails from the family Planorbidae are important freshwater snails due to their low trophic level, and some of them act as intermediate hosts for zoonotic trematodes. There are about 250 species from 40 genera of Planorbidae, but only 14 species from 5 genera (Anisus, Biomphalaria, Bulinus, Gyraulus, and Planorbella) have sequenced complete mitochondrial genomes (mitogenomes). In this study, we sequenced and assembled a high-quality mitogenome of a ramshorn snail, Polypylis sp. TS-2018, which represented the first mitogenome of the genus. The mitogenome of Polypylis sp. TS-2018 is 13,749 bp in length, which is shorter than that of most gastropods. It contains 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and 2 ribosomal RNA (rRNA). We compared mitogenome characteristics, selection pressure, and gene rearrangement among all of the available mitogenomes of ramshorn snails. We found that the nonsynonymous and synonymous substitution rates (Ka/Ks) of most PCGs indicated purifying and negative selection, except for atp8 of Anisus, Biomphalaria, and Gyraulus, which indicated positive selection. We observed that transpositions and reverse transpositions occurred on 10 tRNAs and rrnS, which resulted in six gene arrangement types. We reconstructed the phylogenetic trees using the sequences of PCGs and rRNAs and strongly supported the monophyly of each genus, as well as three tribes in Planorbidae. Both the gene rearrangement and phylogenetic results suggested that Polypylis had a close relationship with Anisus and Gyraulus, while Bulinus was the sister group to all of the other genera. Our results provide useful data for further investigation of species identification, population genetics, and phylogenetics among ramshorn snails.

Phylogenetic relationships and adaptation in deep-sea carideans revealed by mitogenomes.

The deep-sea environment is characterized by extreme and inhospitable conditions, including oxygen depletion, low temperatures, high pressure, absence of light, and limited food availability. Mitochondria and mitogenomes play a crudial role in aerobic respiration to generate energy for eukaryotes. Here, using the Illumina Hiseq 4000 platform, we performed mitogenome sequencing for five deep-sea caridean species: Lebbeus shinkaiae, Lebbeus Formosus, Glyphocrangon regalis, Heterocarpus dorsalis, and Heterocarpus laevigatus, and five deep-sea caridean mitogenomes were assembled and identified. Each of the five mitogenomes contained 13 protein-coding genes, 2 rRNAs and 22 tRNAs. Specific elements, such as tandem repeats and AT-rich sequences, were observed in the control regions of Lebbeus formosus and Lebbeus shinkaiae, potentially take a role in regulating mitochondrial genome replication and transcription. The gene order of all obtained mitogenomes follows caridean ancestral type organization. Phylogenetic analysis shows a robustly supported phylogenetic tree for the infraorder Caridea. The monophyly of the families included in this study was strongly supported. This study supports the monophyly of Oplophoroidea, but rejects the monophyletic status of Nematocarcinoidea, Crangonoidea, and Alpheoidea. At the genus level, Plesionika is polyphyletic and Rimicaris is paraphyletic in our analysis. Furthermore, Paralebbeus may be considered invalid and synonymous with Lebbeus. Positive selection analysis reveals evidence for adaptive changes in the mitogenome of different deep-sea caridean lineages. Nine residues located in cox1, cox3, atp6, nad1, nad2, nad4, nad5, nad6 and cytb were determined to have undergone positive selection. Mitogenome of different deep-sea lineages experienced different positive selection, and the lineage represented by Alvinocarididae living in deep-sea hydrothermal vents experienced the strongest positive selection. This study provides valuable insights into the adaptive evolution of deep-sea shrimps at the mitochondrial, highlighting the mitogenomic strategy that contribute to their unique adaptations in the deep-sea environment.

MINRbase: a comprehensive database of nuclear- and mitochondrial-ribosomal-RNA-derived fragments (rRFs).

We describe the Mitochondrial and Nuclear rRNA fragment database (MINRbase), a knowledge repository aimed at facilitating the study of ribosomal RNA-derived fragments (rRFs). MINRbase provides interactive access to the profiles of 130 238 expressed rRFs arising from the four human nuclear rRNAs (18S, 5.8S, 28S, 5S), two mitochondrial rRNAs (12S, 16S) or four spacers of 45S pre-rRNA. We compiled these profiles by analyzing 11 632 datasets, including the GEUVADIS and The Cancer Genome Atlas (TCGA) repositories. MINRbase offers a user-friendly interface that lets researchers issue complex queries based on one or more criteria, such as parental rRNA identity, nucleotide sequence, rRF minimum abundance and metadata keywords (e.g. tissue type, disease). A 'summary' page for each rRF provides a granular breakdown of its expression by tissue type, disease, sex, ancestry and other variables; it also allows users to create publication-ready plots at the click of a button. MINRbase has already allowed us to generate support for three novel observations: the internal spacers of 45S are prolific producers of abundant rRFs; many abundant rRFs straddle the known boundaries of rRNAs; rRF production is regimented and depends on 'personal attributes' (sex, ancestry) and 'context' (tissue type, tissue state, disease). MINRbase is available at https://cm.jefferson.edu/MINRbase/.

Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA.

The exonuclease ISG20L2 has been initially characterized for its role in the mammalian 5.8S rRNA 3' end maturation, specifically in the cleavage of ITS2 of 12S precursor ribosomal RNA (pre-rRNA). Here, we show that human ISG20L2 is also involved in 18S pre-rRNA maturation through removing the ITS1 region, and contributes to ribosomal biogenesis and cell proliferation. Furthermore, we determined the crystal structure of the ISG20L2 nuclease domain at 2.9 Å resolution. It exhibits the typical αßα fold of the DEDD 3'-5' exonuclease with a catalytic pocket located in the hollow near the center. The catalytic residues Asp183, Glu185, Asp267, His322 and Asp327 constitute the DEDDh motif in ISG20L2. The active pocket represents conformational flexibility in the absence of an RNA substrate. Using structural superposition and mutagenesis assay, we mapped RNA substrate binding residues in ISG20L2. Finally, cellular assays revealed that ISG20L2 is aberrantly up-regulated in colon adenocarcinoma and promotes colon cancer cell proliferation through regulating ribosome biogenesis. Together, these results reveal that ISG20L2 is a new enzymatic member for 18S pre-rRNA maturation, provide insights into the mechanism of ISG20L2 underlying pre-rRNA processing, and suggest that ISG20L2 is a potential therapeutic target for colon adenocarcinoma.

Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives.

Mitochondrial-derived peptides (MDPs) are a novel class of bioactive microproteins encoded by short open-reading frames (sORF) in mitochondrial DNA (mtDNA). Currently, three types of MDPs have been identified: Humanin (HN), MOTS-c (Mitochondrial ORF within Twelve S rRNA type-c), and SHLP1-6 (small Humanin-like peptide, 1 to 6). The 12 S ribosomal RNA (MT-RNR1) gene harbors the sequence for MOTS-c, whereas HN and SHLP1-6 are encoded by the 16 S ribosomal RNA (MT-RNR2) gene. Special genetic codes are used in mtDNA as compared to nuclear DNA: (i) ATA and ATT are used as start codons in addition to the standard start codon ATG; (ii) AGA and AGG are used as stop codons instead of coding for arginine; (iii) the standard stop codon UGA is used to code for tryptophan. While HN, SHLP6, and MOTS-c are encoded by the H (heavy owing to high guanine + thymine base composition)-strand of the mtDNA, SHLP1-5 are encoded by the L (light owing to less guanine + thymine base composition)-strand. MDPs attenuate disease pathology including Type 1 diabetes (T1D), Type 2 diabetes (T2D), gestational diabetes, Alzheimer's disease (AD), cardiovascular diseases, prostate cancer, and macular degeneration. The current review will focus on the MDP regulation of T2D, T1D, and gestational diabetes along with an emphasis on the evolutionary pressures for conservation of the amino acid sequences of MDPs.

Roles of rRNA N-methyladenosine modification in the function of ribosomes.

The N-methyladenosine (m6A) modification of ribosomal RNA (rRNA) plays critical roles in regulating the function of ribosomes, the essential molecular machines that translate genetic information from mRNA into proteins. Specifically, m6A modification affects ribosome biogenesis, stability, and function by regulating the processing and maturation of rRNA, the assembly and composition of ribosomes, and the accuracy and efficiency of translation. Furthermore, m6A modification allows for dynamic regulation of translation in response to environmental and cellular signals. Therefore, a deeper understanding of the mechanisms and functions of m6A modification in rRNA will advance our knowledge of ribosome-mediated gene expression and facilitate the development of new therapeutic strategies for ribosome-related diseases.

The Effects of Deregulated Ribosomal Biogenesis in Cancer.

Ribosomes are macromolecular ribonucleoprotein complexes assembled from RNA and proteins. Functional ribosomes arise from the nucleolus, require ribosomal RNA processing and the coordinated assembly of ribosomal proteins (RPs), and are frequently hyperactivated to support the requirement for protein synthesis during the self-biosynthetic and metabolic activities of cancer cells. Studies have provided relevant information on targeted anticancer molecules involved in ribosome biogenesis (RiBi), as increased RiBi is characteristic of many types of cancer. The association between unlimited cell proliferation and alterations in specific steps of RiBi has been highlighted as a possible critical driver of tumorigenesis and metastasis. Thus, alterations in numerous regulators and actors involved in RiBi, particularly in cancer, significantly affect the rate and quality of protein synthesis and, ultimately, the transcriptome to generate the associated proteome. Alterations in RiBi in cancer cells activate nucleolar stress response-related pathways that play important roles in cancer-targeted interventions and immunotherapies. In this review, we focus on the association between alterations in RiBi and cancer. Emphasis is placed on RiBi deregulation and its secondary consequences, including changes in protein synthesis, loss of RPs, adaptive transcription and translation, nucleolar stress regulation, metabolic changes, and the impaired ribosome biogenesis checkpoint.

Comparative mitochondrial genome analysis of three leafhopper species of the genus Abrus Dai & Zhang (Hemiptera: Cicadellidae: Deltocephalinae) from China with phylogenetic implication.

BACKGROUND: The phylogenetic position and classification of Athysanini are poorly defined, as it includes a large group of polyphyletic genera that have historically been assigned to it mainly because they still exhibit the most typical deltocephaline genitalic and external body characters but lack the distinctive characteristics that other tribes possess. The bamboo-feeding leafhopper genus Abrus belong to the tribe Athysanini of subfamily Deltocephalinae, which currently comprises 19 valid described species, and are limited to the Oriental and Palaearctic regions in China. Although the taxonomy of Abrus are well updated, the references on comparative mitogenomic analyses of Abrus species are only known for a single species. In this study, we sequenced and analyzed the complete mitochondrial genomes (mitogenomes) of Abrus daozhenensis Chen, Yang & Li, 2012 (16,391bp) and A. yunshanensis Chen, Yang & Li, 2012 (15,768bp) (Athysanini), and compared with published mitogenome sequence of A. expansivus Xing & Li, 2014 (15,904bp). RESULTS: These Abrus species shared highly conserved mitogenomes with similar gene order to that of the putative ancestral insect with 37 typical genes and a non-coding A + T-rich region. The nucleotide composition of these genomes is highly biased toward A + T nucleotides (76.2%, 76.3%, and 74.7%), AT-skews (0.091 to 0.095, and 0.095), negative GC-skews (- 0.138, - 0.161, and - 0.138), and codon usage. All 22 tRNA genes had typical cloverleaf secondary structures, except for trnS1 (AGN) which lacks the dihydrouridine arm, and distinctively trnG in the mitogenome of A. expansivus lacks the TψC arm. Phylogenetic analyses based on 13 PCGs, 2 rRNA genes, and 22 tRNA genes consistently recovered the monophyletic Opsiini, Penthimiini, Selenocephalini, Scaphoideini, and Athysanini (except Watanabella graminea, previously sequenced species as Chlorotettix nigromaculatus) based on limited available mitogenome sequence data of 37 species. CONCLUSION: At present, Abrus belongs to the tribe Athysanini based on both morphological and molecular datasets, which is strongly supported in present phylogenetic analyses in both BI and ML methods using the six concatenated datasets: amino acid sequences and nucleotides from different combinations of protein-coding genes (PCGs), ribosomal RNA (rRNAs), and transfer RNA (tRNAs). Phylogenetic trees reconstructed herein based on the BI and ML analyses consistently recovered monophylitic Athysanini, except Watanabella graminea (Athysanini) in Opsiini with high support values.

The antiproliferative effect of FGF2 in K-Ras-driven tumor cells involves modulation of rRNA and the nucleolus.

The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response to stress signals. Despite being a growth factor, FGF2 has antiproliferative and tumor-suppressive functions in some cellular contexts. In this work, we investigated how the antiproliferative effect of FGF2 modulates chromatin-, nucleolus- and rDNA-associated proteins. The chromatin and nucleolar proteome indicated that FGF2 stimulation modulates proteins related to transcription, rRNA expression and chromatin-remodeling proteins. The global transcriptional rate and nucleolus area increased along with nucleolar disorganization upon 24 h of FGF2 stimulation. FGF2 stimulation induced immature rRNA accumulation by increasing rRNA transcription. The rDNA-associated protein analysis reinforced that FGF2 stimulus interferes with transcription and rRNA processing. RNA Pol I inhibition partially reversed the growth arrest induced by FGF2, indicating that changes in rRNA expression might be crucial for triggering the antiproliferative effect. Taken together, we demonstrate that the antiproliferative FGF2 stimulus triggers significant transcriptional changes and modulates the main cell transcription site, the nucleolus.

Downregulation of ribosomal RNA (rRNA) genes in human head and neck squamous cell carcinoma (HNSCC) cells correlates with rDNA promoter hypermethylation.

Eukaryotes carry hundreds of ribosomal RNA (rRNA) genes as tandem arrays, which generate rRNA for protein synthesis. Humans carry âˆ¼ 400 rRNA gene copies and their expression is epigenetically regulated. Dysregulation of rRNA synthesis and ribosome biogenesis are characteristic features of cancers. Targeting aberrant rRNA expression for cancer therapy is being explored. Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent cancers globally. Using quantitative PCR and bisulfite sequencing, we show that rRNA genes are downregulated and their promoters are hypermethylated in HNSCC cell lines. These findings may have relevance for prognosis and diagnosis of HNSCC.

Comprehensive identification of diverse ribosomal RNA modifications by targeted nanopore direct RNA sequencing and JACUSA2.

Ribosomal RNAs are decorated by numerous post-transcriptional modifications whose exact roles in ribosome biogenesis, function, and human pathophysiology remain largely unknown. Here, we report a targeted direct rRNA sequencing approach involving a substrate selection step and demonstrate its suitability to identify differential modification sites in combination with the JACUSA2 software. We compared JACUSA2 to other tools designed for RNA modification detection and show that JACUSA2 outperforms other software with regard to detection of base modifications such as methylation, acetylation and aminocarboxypropylation. To illustrate its widespread usability, we applied our method to a collection of CRISPR-Cas9 engineered colon carcinoma cells lacking specific enzymatic activities responsible for particular rRNA modifications and systematically compared them to isogenic wild-type RNAs. Besides the numerous 2'-O methylated riboses and pseudouridylated residues, our approach was suitable to reliably identify differential base methylation and acetylation events. Importantly, our method does not require any prior knowledge of modification sites or the need to train complex models. We further report for the first time detection of human rRNA modifications by direct RNA-sequencing on Flongle flow cells, the smallest-scale nanopore flow cell available to date. The use of these smaller flow cells reduces RNA input requirements, making our workflow suitable for the analysis of samples with limited availability and clinical work.

The induction of p53 correlates with defects in the production, but not the levels, of the small ribosomal subunit and stalled large ribosomal subunit biogenesis.

Ribosome biogenesis is one of the biggest consumers of cellular energy. More than 20 genetic diseases (ribosomopathies) and multiple cancers arise from defects in the production of the 40S (SSU) and 60S (LSU) ribosomal subunits. Defects in the production of either the SSU or LSU result in p53 induction through the accumulation of the 5S RNP, an LSU assembly intermediate. While the mechanism is understood for the LSU, it is still unclear how SSU production defects induce p53 through the 5S RNP since the production of the two subunits is believed to be uncoupled. Here, we examined the response to SSU production defects to understand how this leads to the activation of p53 via the 5S RNP. We found that p53 activation occurs rapidly after SSU production is blocked, prior to changes in mature ribosomal RNA (rRNA) levels but correlated with early, middle and late SSU pre-rRNA processing defects. Furthermore, both nucleolar/nuclear LSU maturation, in particular late stages in 5.8S rRNA processing, and pre-LSU export were affected by SSU production defects. We have therefore uncovered a novel connection between the SSU and LSU production pathways in human cells, which explains how p53 is induced in response to SSU production defects.

Isocitrate dehydrogenase wt and IDHmut adult-type diffuse gliomas display distinct alterations in ribosome biogenesis and 2'O-methylation of ribosomal RNA.

BACKGROUND: High-grade adult-type diffuse gliomas (HGGs) constitute a heterogeneous group of aggressive tumors that are mostly incurable. Recent advances highlighting the contribution of ribosomes to cancer development have offered new clinical perspectives. Here, we uncovered that isocitrate dehydrogenase (IDH)wt and IDHmut HGGs display distinct alterations of ribosome biology, in terms of rRNA epitranscriptomics and ribosome biogenesis, which could constitute novel hallmarks that can be exploited for the management of these pathologies. METHODS: We analyzed (1) the ribosomal RNA 2'O-ribose methylation (rRNA 2'Ome) using RiboMethSeq and in-house developed bioinformatics tools (https://github.com/RibosomeCRCL/ribomethseq-nfandrRMSAnalyzer) on 3 independent cohorts compiling 71 HGGs (IDHwt n = 30, IDHmut n = 41) and 9 non-neoplastic samples, (2) the expression of ribosome biogenesis factors using medium throughput RT-qPCR as a readout of ribosome biogenesis, and (3) the sensitivity of 5 HGG cell lines to RNA Pol I inhibitors (CX5461, BMH-21). RESULTS: Unsupervised analysis demonstrated that HGGs could be distinguished based on their rRNA 2'Ome epitranscriptomic profile, with IDHwt glioblastomas displaying the most significant alterations of rRNA 2'Ome at specific sites. In contrast, IDHmut HGGs are largely characterized by an overexpression of ribosome biogenesis factors compared to non-neoplastic tissues or IDHwt glioblastomas. Finally, IDHmut HGG-derived spheroids display higher cytotoxicity to CX5461 than IDHwt glioblastoma, while all HGG spheroids display a similar cytotoxicity to BMH-21. CONCLUSIONS: In HGGs, IDH mutational status is associated with specific alterations of the ribosome biology and with distinct sensitivities to RNA Pol I inhibitors.

Synthesis of the ribosomal RNA precursor in human cells: mechanisms, factors and regulation.

The ribosomal RNA precursor (pre-rRNA) comprises three of the four ribosomal RNAs and is synthesized by RNA polymerase (Pol) I. Here, we describe the mechanisms of Pol I transcription in human cells with a focus on recent insights gained from structure-function analyses. The comparison of Pol I-specific structural and functional features with those of other Pols and with the excessively studied yeast system distinguishes organism-specific from general traits. We explain the organization of the genomic rDNA loci in human cells, describe the Pol I transcription cycle regarding structural changes in the enzyme and the roles of human Pol I subunits, and depict human rDNA transcription factors and their function on a mechanistic level. We disentangle information gained by direct investigation from what had apparently been deduced from studies of the yeast enzymes. Finally, we provide information about how Pol I mutations may contribute to developmental diseases, and why Pol I is a target for new cancer treatment strategies, since increased rRNA synthesis was correlated with rapidly expanding cell populations.

Interactions between terminal ribosomal RNA helices stabilize the E. coli large ribosomal subunit.

The ribosome is a large ribonucleoprotein assembly that uses diverse and complex molecular interactions to maintain proper folding. In vivo assembled ribosomes have been isolated using MS2 tags installed in either the 16S or 23S ribosomal RNAs (rRNAs), to enable studies of ribosome structure and function in vitro. RNA tags in the Escherichia coli 50S subunit have commonly been inserted into an extended helix H98 in 23S rRNA, as this addition does not affect cellular growth or in vitro ribosome activity. Here, we find that E. coli 50S subunits with MS2 tags inserted in H98 are destabilized compared to wild-type (WT) 50S subunits. We identify the loss of RNA-RNA tertiary contacts that bridge helices H1, H94, and H98 as the cause of destabilization. Using cryogenic electron microscopy (cryo-EM), we show that this interaction is disrupted by the addition of the MS2 tag and can be restored through the insertion of a single adenosine in the extended H98 helix. This work establishes ways to improve MS2 tags in the 50S subunit that maintain ribosome stability and investigates a complex RNA tertiary structure that may be important for stability in various bacterial ribosomes.

The complete mitochondrial genomes of four lagriine species (Coleoptera, Tenebrionidae) and phylogenetic relationships within Tenebrionidae.

It is common to use whole mitochondrial genomes to analyze phylogenetic relationships among insects. In this study, seven mitogenomes of Tenebrionidae are newly sequenced and annotated. Among them, four species (Cerogira janthinipennis (Fairmaire, 1886), Luprops yunnanus (Fairmaire, 1887), Anaedus unidentasus Wang & Ren, 2007, and Spinolyprops cribricollis Schawaller, 2012) represent the subfamily Lagriinae. In this subfamily, the mitogenomes of the tribes Goniaderini (A. unidentasus) and Lupropini (L. yunnanus and S. cribricollis) were first reported; they were found to be 15,328-16,437 bp in length and encode 37 typical mitochondrial genes (13 PCGs, 2 rRNAs, 22 tRNAs, and a single noncoding control region). Most protein-coding genes in these mitogenomes have typical ATN start codons and TAR or an incomplete stop codon T-. In these four lagriine species, F, L2, I, and N are the most frequently used amino acids. In the 13 PCGs, the gene atp8 (Pi = 0.978) was the most diverse nucleotide, while cox1 was the most conserved gene with the lowest value (Pi = 0.211). The phylogenetic results suggest that Pimelinae, Lagriinae, Blaptinae, Stenochiinae, and Alleculinae are monophyletic, Diaperinae is paraphyletic, and Tenebrioninae appears polyphyletic. In Lagriinae, the tribe Lupropini appears paraphyletic because Spinolyprops is clustered with Anaedus in Goniaderini. These mitogenomic data provide important molecular data for the phylogeny of Tenebrionidae.

[The Structure, Expression, and Non-Canonical Functions of Human rDNA: The Role of Non-Coding Regions].

The genes coding for the rRNAs seem evolutionary conserved on the first glance, but astonish one with their variability in the structure and a variety of functions on closer examination. The non-coding parts of rDNA contain regulatory elements, protein binding sites, pseudogenes, repetitive sequences, and microRNA genes. Ribosomal intergenic spacers are not only in charge with the nucleolus morphology and functioning, namely, the rRNA expression and ribosome biogenesis, but also control nuclear chromatin formation thus mediating cell differentiation. The alterations in the expression of these non-coding regions of rDNA in response to environmental stimuli underlie the keen sense of a cell to various types of stressors. Malfunctioning of this process may result in a wide range of pathologies from oncology to neurodegenerative disease and mental illness. Here, we observe to-date materials on the structure and transcription of the ribosomal intergenic spacer in humans and its role in rRNA expression, in-born disease development, and cancer.