ncRNA Genes Research Articles

POS0349 SEQUENCE COMPLEMENTARITY BETWEEN SARS-CoV-2 GENOME AND HUMAN NONCODING RNAS ASSOCIATED WITH IMMUNOLOGICAL DISORDERS: AN IN SILICO PIVOTAL STUDY

Background:Recent evidence shows that human cells may produce several noncoding (nc)RNAs in response to viral infections. Among them, a central role has been attributed to long noncoding (lnc)RNAs, more than 200 nucleotides in length, which are also crucially involved in cancer and autoimmunity. LncRNAs epigenetically control the transcription of genes presiding over cell proliferation, differentiation, migration and apoptosis, by directly or indirectly binding cellular or foreign nucleic acids, including viral genomes.Objectives:The objectives of this study were to evaluate in silico the presence of a nucleotide sequence complementarity between the RNA genome of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and human ncRNA genes and to analyze any associations between SARS-CoV-2 gene-matching ncRNAs and human diseases.Methods:The FASTA sequence of each of the 11 SARS-CoV-2 isolate Wuhan-Hu-1 genes (ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, S, E, M, N) was retrieved from NCBI.nlm.nih.gov/gene (reference sequence NC_045512.2). The ensembl.org library for human ncRNA genes was interrogated for any base-pair match and detected human ncRNAs analyzed for their functional activity. Finally, the associations between ncRNAs and human diseases were searched on GWAS databases (https://www.ebi.ac.uk/gwas and https://www.genecards.org).Results:A total of 252 matches between SARS-CoV-2 genes and human ncRNAs were recorded (ORF1ab: 28; ORF3a: 9; ORF6: 50; ORF7a: 31; ORF7b: 16; ORF8: 23; ORF10: 5; S: 24; E: 17; M: 32; N: 17). With the exception of two small nuclear RNAs (RNVU1-4 and RNU4-74P corresponding to ORF6 and ORF10, respectively), all of them were lncRNAs, mostly expressed in testis and central nervous system under physiological conditions. Percentage of alignment ranged from 91.30% to 100%, with a mean nucleotide alignment length of 17.5±2.4. Polymorphic variants of these transcripts have mostly been reported in patients with neuropsychiatric disorders, cancer and dysmetabolism. Of note, we found 13 and 15 complementarities with lncRNAs associated with immune-mediated diseases Table 1. and immunological pathways (IL-2, IL-6, IL-12, IL-12R, IL-13, IL-17, M-CSF, CXCL-10, TRAIL-R2 and IgG glycosylation), respectively.Conclusion:This pivotal study shows that SARS-CoV-2 genes contain complementary sequences to human ncRNAs in turn associated with several diseases, including autoimmunity. The biological effects of this interaction remain to be elucidated.Table 1.SARS-CoV-2 complementary ncRNAs and associated immunological disordersSARS-CoV-2 geneLncRNAGenomic locationNucleotide alignment lengthAlignment percentageAssociated immunological disorderSXACTX:113705866-11370588318100%Crohn’s diseaseNLINC013581:59082428-5908257417100%Acute Graft-versus-Host DiseaseECOX10-AS117:14029229-1402924517100%Systemic lupus erythematosusORF8AC093765.34:116752764-1167527842195.24%Ulcerative colitisORF6CDKN2B-AS19:22033529-2203354618100%Multiple sclerosisCHROMR2:178433948-1784339682195.24%Multiple sclerosisPsoriasisAtopic eczemaWAKMAR26:137857643-13785765715100%Atopic eczemaHay feverAllergic rhinitisMultiple sclerosisPsoriasisSystemic sclerosisSystemic lupus erythematosusRheumatoid arthritisAC008691.15:159362809-159362828(promoter flank)2095%SarcoidosisPsoriasisPsoriatic arthritisSclerosing cholangitisCeliac diseaseType I diabetes mellitusSystemic lupus erythematosusJuvenile idiopathic arthritisUlcerative colitisCrohn’s diseaseTakayasu arteritisMultiple sclerosisLMCD1-AS13:7953602-7953616(enhancer)15100%Systemic sclerosisMLINC019342:181403969-18140398416100%Multiple sclerosisAnkylosing spondylitisCeliac diseaseRheumatoid arthritisORF7bXACTX:113959816-11395983116100%Crohn’s diseaseLINC0262110:62289643-6230233515100%Rheumatoid arthritisLINC019913:187966255-18796626915100%IgA deficitAtopic asthmaAllergic rhinitisDisclosure of Interests:None declared

Tetraarsenic oxide affects non-coding RNA transcriptome through deregulating polycomb complexes in MCF7 cells

Non-coding RNAs (ncRNAs) play important and diverse roles in mammalian cell biology and pathology. Although the functions of an increasing number of ncRNAs have been identified, the mechanisms underlying ncRNA gene expression remain elusive and are incompletely understood. Here, we investigated ncRNA gene expression in Michigan cancer foundation 7 (MCF7), a malignant breast cancer cell line, on treatment of tetraarsenic oxide (TAO), a potential anti-cancer drug. Our genomic analyses found that TAO up- or down-regulated ncRNA genes genome-wide. A subset of identified ncRNAs with critical biological and clinical functions were validated by real-time quantitative polymerase chain reaction. Intriguingly, these TAO-regulated genes included CDKN2B-AS, HOXA11-AS, SHH, and DUSP5 that are known to interact with or be targeted by polycomb repressive complexes (PRCs). In addition, the PRC subunits were enriched in these TAO-regulated ncRNA genes and TAO treatment deregulated the expression of PRC subunits. Strikingly, TAO decreased the cellular and gene-specific levels of EZH2 expression and H3K27me3. In particular, TAO reduced EZH2 and H3K27me3 and increased transcription at MALAT1 gene. Inhibiting the catalytic activity of EZH2 using GSK343 increased representative TAO-inducible ncRNA genes. Together, our findings suggest that the expression of a subset of ncRNA genes is regulated by PRC2 and that TAO could be a potent epigenetic regulator through PRCs to modulate the ncRNA gene expression in MCF7 cells.

GeneCaRNA: A Comprehensive Gene-centric Database of Human Non-coding RNAs in the GeneCards Suite

Non-coding RNA (ncRNA) genes assume increasing biological importance, with growing associations with diseases. Many ncRNA sources are transcript-centric, but for non-coding variant analysis and disease decipherment it is essential to transform this information into a comprehensive set of genome-mapped ncRNA genes. We present GeneCaRNA, a new all-inclusive gene-centric ncRNA database within the GeneCards Suite. GeneCaRNA information is integrated from four community-backed data structures: the major transcript database RNAcentral with its 20 encompassed databases, and the ncRNA entries of three major gene resources HGNC, Ensembl and NCBI Gene. GeneCaRNA presents 219,587 ncRNA gene pages, a 7-fold increase from those available in our three gene mining sources. Each ncRNA gene has wide-ranging annotation, mined from >100 worldwide sources, providing a powerful GeneCards-leveraged search. The latter empowers VarElect, our disease-gene interpretation tool, allowing one to systematically decipher ncRNA variants. The combined power of GeneCaRNA with GeneHancer, our regulatory elements database, facilitates wide-ranging scrutiny of the non-coding terra incognita of gene networks and whole genome analyses.

Impact of paternal exercise on physiological systems in the offspring

A significant number of studies have demonstrated that paternal exercise modulates future generations via effects on the sperm epigenome. However, comprehensive information regarding the effects of exercise performed by the father on different tissues and their clinical relevance has not yet been explored in detail. This narrative review is focused on the effects of paternal exercise training on various physiological systems of offspring. A detailed mechanistic understanding of these effects could provide crucial clues for the exercise physiology field and aid the development of therapeutic approaches to mitigate disorders in future generations. Non-coding RNA and DNA methylation are major routes for transmitting epigenetic information from parents to offspring. Resistance and treadmill exercise are the most frequently used modalities of planned and structured exercise in controlled experiments. Paternal exercise orchestrated protective effects over changes in fetus development and placenta inflammatory status. Moreover paternal exercise promoted modifications in the ncRNA profiles, gene and protein expression in the hippocampus, left ventricle, skeletal muscle, tendon, liver and pancreas in the offspring, while the transgenerational effects are unknown. Paternal exercise demonstrates clinical benefits to the offspring and provides a warning on the harmful effects of a paternal unhealthy lifestyle. Exercise in fathers is presented as one of the most logical and cost-effective ways of restoring health in the offspring and, consequently, modifying the phenotype. It is important to consider that paternal programming might have unique significance in the developmental origins of offspring diseases.

Mutant non-coding RNA resource in mouse embryonic stem cells.

ABSTRACTGene trapping is a high-throughput approach that has been used to introduce insertional mutations into the genome of mouse embryonic stem (ES) cells. It is performed with generic gene trap vectors that simultaneously mutate and report the expression of the endogenous gene at the site of insertion and provide a DNA sequence tag for the rapid identification of the disrupted gene. Large-scale international efforts assembled a gene trap library of 566,554 ES cell lines with single gene trap integrations distributed throughout the genome. Here, we re-investigated this unique library and identified mutations in 2202 non-coding RNA (ncRNA) genes, in addition to mutations in 12,078 distinct protein-coding genes. Moreover, we found certain types of gene trap vectors preferentially integrating into genes expressing specific long non-coding RNA (lncRNA) biotypes. Together with all other gene-trapped ES cell lines, lncRNA gene-trapped ES cell lines are readily available for functional in vitro and in vivo studies.

Systematic prediction of genes functionally associated with bacterial retrons and classification of the encoded tripartite systems.

Bacterial retrons consist of a reverse transcriptase (RT) and a contiguous non-coding RNA (ncRNA) gene. One third of annotated retrons carry additional open reading frames (ORFs), the contribution and significance of which in retron biology remains to be determined. In this study we developed a computational pipeline for the systematic prediction of genes specifically associated with retron RTs based on a previously reported large dataset representative of the diversity of prokaryotic RTs. We found that retrons generally comprise a tripartite system composed of the ncRNA, the RT and an additional protein or RT-fused domain with diverse enzymatic functions. These retron systems are highly modular, and their components have coevolved to different extents. Based on the additional module, we classified retrons into 13 types, some of which include additional variants. Our findings provide a basis for future studies on the biological function of retrons and for expanding their biotechnological applications.

Histone sumoylation promotes Set3 histone-deacetylase complex-mediated transcriptional regulation.

Histones are substrates of the SUMO (small ubiquitin-like modifier) conjugation pathway. Several reports suggest histone sumoylation affects transcription negatively, but paradoxically, our genome-wide analysis shows the modification concentrated at many active genes. We find that trans-tail regulation of histone-H2B ubiquitylation and H3K4 di-methylation potentiates subsequent histone sumoylation. Consistent with the known control of the Set3 histone deacetylase complex (HDAC) by H3K4 di-methylation, histone sumoylation directly recruits the Set3 complex to both protein-coding and noncoding RNA (ncRNA) genes via a SUMO-interacting motif in the HDAC Cpr1 subunit. The altered gene expression profile caused by reducing histone sumoylation matches well to the profile in cells lacking Set3. Histone H2B sumoylation and the Set3 HDAC coordinately suppress cryptic ncRNA transcription initiation internal to mRNA genes. Our results reveal an elaborate co-transcriptional histone crosstalk pathway involving the consecutive ubiquitylation, methylation, sumoylation and deacetylation of histones, which maintains transcriptional fidelity by suppressing spurious transcription.

CAGE-seq analysis of osteoblast derived from cleidocranial dysplasia human induced pluripotent stem cells.

Non-coding RNAs (ncRNAs) comprise a major portion of transcripts and serve an essential role in biological processes. Although the importance of major transcriptomes in osteogenesis has been extensively studied, the function of ncRNAs in human osteogenesis remains unclear. Previously, we developed hiPSCs from patients with cleidocranial dysplasia (CCD) caused by runt-related transcription factor 2 (RUNX2) haploinsufficiency. To gain insight into ncRNAs in osteogenesis, we surveyed differential ncRNA expression profiling and promoter differences of RUNX2 using patient-specific iPSCs and cap analysis gene expression (CAGE) technology to define the promoter landscape. Revertant iPSCs (Rev1 iPSCs) edited by CRISPR/Cas9 system to harbor mutation-corrected RUNX2 exhibited increased proximal promoter expression of RUNX2, while CCD iPSCs did not. We identified 2271 ncRNA genes with altered expression levels before and after differentiation, 31 of which showed at least 20-fold higher expression in Rev1 iPSCs. Bioinformatic analysis also categorized AC007392.3, LINC00379, RP11-122D10.1, and RP11-90J7.2 as enhancer regulatory regions, and HOXA-AS2, MIR219-2, and RP11-834C11.3 as dyadic regulatory regions of these ncRNAs. In addition, two miRNAs, termed MIR199A2 and MIR152, were found to have high enrichment of osteogenic-related terms. Upon further examination of the role of MIR152 on osteoblast differentiation, we found that MIR152 knockdown induced upregulation of ALP and COL1A1 in Saos-2 cells. Thus, ncRNAs were found to regulate the osteogenic differentiation potentials of hiPSCs that are used for bone regeneration and repair owing to their differentiation potentials. These data allow understanding ncRNA profiles of hiPSCs during osteogenesis.

Degradation of Non-coding RNAs Promotes Recycling of Termination Factors at Sites of Transcription

A large share of the non-coding transcriptome in yeast is controlled by the Nrd1-Nab3-Sen1 (NNS) complex, which promotes transcription termination of non-coding RNA (ncRNA) genes, and by the nuclear exosome, which limits the steady-state levels of the transcripts produced. How unconstrained ncRNA levels affect RNA metabolism and gene expression are long-standing and important questions. Here, we show that degradation of ncRNAs by the exosome is required for freeing Nrd1 and Nab3 from the released transcript after termination. In exosome mutants, these factors are sequestered by ncRNAs and cannot be efficiently recycled to sites of transcription, inducing termination defects at NNS targets. ncRNA-dependent, genome-wide termination defects can be recapitulated by the expression of a degradation-resistant, circular RNA containing a natural NNS target in exosome-proficient cells. Our results have important implications for the mechanism of termination, the general impact of ncRNAs abundance, and the importance of nuclear ncRNA degradation.

Cytogenetic Mapping of 35 New Markers in the Alpaca (Vicugna pacos).

Alpaca is a camelid species of broad economic, biological and biomedical interest, and an essential part of the cultural and historical heritage of Peru. Recently, efforts have been made to improve knowledge of the alpaca genome, and its genetics and cytogenetics, to develop molecular tools for selection and breeding. Here, we report cytogenetic mapping of 35 new markers to 19 alpaca autosomes and the X chromosome. Twenty-eight markers represent alpaca SNPs, of which 17 are located inside or near protein-coding genes, two are in ncRNA genes and nine are intergenic. The remaining seven markers correspond to candidate genes for fiber characteristics (BMP4, COL1A2, GLI1, SFRP4), coat color (TYR) and development (CHD7, PAX7). The results take the tally of cytogenetically mapped markers in alpaca to 281, covering all 36 autosomes and the sex chromosomes. The new map assignments overall agree with human–camelid conserved synteny data, except for mapping BMP4 to VPA3, suggesting a hitherto unknown homology with HSA14. The findings validate, refine and correct the current alpaca assembly VicPac3.1 by anchoring unassigned sequence scaffolds, and ordering and orienting assigned scaffolds. The study contributes to the improvement in the alpaca reference genome and advances camelid molecular cytogenetics.

The rare lncRNA GOLLD is widespread and structurally conserved among Mycobacterium tRNA arrays

ABSTRACT Noncoding RNA (ncRNA) genes produce transcripts involved in a wide range of functions, including catalytic and regulatory functions. Besides, some transcripts have highly complex structures that may impact their activities. Among the largest bacterial ncRNAs, there is the rare GOLLD RNA, which is associated with tRNA genes and supposed to be chromosome- and phage-encoded in specialized groups of bacteria, including those from Lactobacillales and Actinomycetales orders. The only GOLLD structure was inferred from a variety of sequences, including many marine metagenomes. To explore GOLLD RNA in bacterial genomes, we mined the GOLLD gene in thousands of Mycobacterium and virus genomes using Infernal software. We identified this gene in 350 mycobacteria, including megaplasmids, and 39 bacteriophages, mainly in the genomic context of tRNA arrays. Mycobacterium GOLLD genes presented a high diversity and were distributed in three phylogenetic groups: (i) Mycobacterium exclusive; (ii) Mycobacterium and mycobacteriophages; and (iii) mycobacteriophage exclusive. We also determined the GOLLD secondary structure of each group using R2 R software based on GOLLD alignments generated by Infernal software. All GOLLD groups displayed a 3ʹ half conserved structure, including utter E-loops pseudoknots substructures, also shared by non-Mycobacterium GOLLD while the 5ʹ half motif was different among the groups. Here, we showed that the lncRNA GOLLD is widespread in Mycobacterium within tRNA arrays and corroborated the previously predicted GOLLD secondary structure.

Gene Expression Level and Gene Set Enrichment Analysis of Host Genes

Genome-wide analysis has shown that there are non-protein-coding RNAs (ncRNAs) that are localized on intronic regions of protein-coding genes. The intronic ncRNAs are hosted in introns of protein-coding genes that are referred to as host genes. Our previous study reported genomic features of intronic ncRNA genes and host genes. However, transcriptomic features of host genes have not been investigated. Here we report gene expression level analysis of host genes and investigate biological functions of host genes. Our results showed that gene expression levels of host genes tend to be higher than those of non-host genes. Host genes orthologous between human and mouse have more conserved expression levels than non-host orthologous genes. And host genes with high expression levels involve nervous system, gene expression, protein modification and cytoskeleton whereas there were mostly no enriched biological functions in host genes with low expression levels. These results suggest that host genes have characteristic transcript quantification and biological functions. The characteristics may be useful for further analysis of regulatory ways of host gene expression.

Complete Genome Sequence of Pantoea ananatis Strain NN08200, an Endophytic Bacterium Isolated from Sugarcane

Stain NN08200 was isolated from the surface-sterilized stem of sugarcane grown in Guangxi province of China. The stain was Gram-negative, facultative anaerobic, non-spore-forming bacteria. The complete genome SNP-based phylogenetic analysis indicate that NN08200 is a member of the genus Pantoea ananatis. Here, we summarize the features of strain NN08200 and describe its complete genome. The genome contains a chromosome and two plasmids, in total 5,176,640 nucleotides with 54.76% GC content. The chromosome genome contains 4598 protein-coding genes, and 135 ncRNA genes, including 22 rRNA genes, 78 tRNA genes and 35 sRNA genes, the plasmid 1 contains 149 protein-coding genes and the plasmid 2 contains 308 protein-coding genes. We identified 130 tandem repeats, 101 transposon genes, and 16 predicted genomic islands on the chromosome. We found an indole pyruvate decarboxylase encoding gene which involved in the biosynthesis of the plant hormone indole-3-acetic acid, it may explain the reason why NN08200 stain have growth-promoting effects on sugarcane. Considering the pathogenic potential and its versatility of the species of the genus Pantoea, the genome information of the strain NN08200 give us a chance to determine the genetic background of interactions between endophytic enterobacteria and plants.

Distribution Patterns of DNA N6-Methyladenosine Modification in Non-coding RNA Genes.

N6-methyladenosine (6mA) DNA modification played an important role in epigenetic regulation of gene expression. And the aberrational expression of non-coding genes, as important regular elements of gene expression, was related to many diseases. However, the distribution and potential functions of 6mA modification in non-coding RNA (ncRNA) genes are still unknown. In this study, we analyzed the 6mA distribution of ncRNA genes and compared them with protein-coding genes in four species (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens) using single-molecule real-time (SMRT) sequencing data. The results indicated that the consensus motifs of short nucleotides at 6mA location were highly conserved in four species, and the non-coding gene was less likely to be methylated compared with protein-coding gene. Especially, the 6mA-methylated lncRNA genes were expressed significant lower than genes without methylation in A. thaliana (p = 3.295e-4), D. melanogaster (p = 3.439e-11), and H. sapiens (p = 9.087e-3). The detection and distribution profiling of 6mA modification in ncRNA regions from four species reveal that 6mA modifications may have effects on their expression level.

LOC646329 long non-coding RNA sponges miR-29b-1 and regulates TGFβ signaling in colorectal cancer.

Non-coding RNAs (ncRNAs) are reported to be regulators of signaling pathways that are involved in colorectal cancer (CRC) progression. Aiming at finding ncRNAs (miRNAs) that are differentially expressed in tumor versus normal colorectal tissue samples, online RNA-seq data were analyzed. Of between 18 candidate miRNAs, hsa-miR-29b-1 (miR-29b-1) represented the highest fold change of expression level. Hsa-miR-29b-1 is encoded from the third intron of LOC646329 long ncRNA gene. Surprisingly, two miR-29b sponging sites were predicted within exons of LOC646329 gene. Then, dual luciferase assay supported the interaction of miR-29b-1 with LOC646329-variant D transcript. Also, a direct indication of miR-29b-1 with 3'UTR sequence of SMAD3 gene was verified through dual luciferase assay and RT-qPCR analysis. Furthermore, a reverse pattern of expression was detected between miR-29b-1 and LOC646329-variant D transcript in about 25 pairs of CRC tumor samples, detected by RTqPCR. Consistently, overexpression of LOC646329-variant D transcript was followed by increased SMAD3 and p21 genes expression level and downregulation of CyclinD1 genes in HCT116 cells, detected by RT-qPCR, and western analysis. Also, overexpression of it was followed by increased G1 cell population of HCT-116 cells. All of these data suggested a tumor suppressor effect for LOC646329-variant D in CRC tumor tissue samples, consistent to its reduced expression level at late stages of CRC progression. Data also indicated that LOC646329-variant D exerts its suppression effect on CRC progression through sponging miR-29b, which in turn regulates Wnt and TGFB signaling pathways. This makes LOC646329-variant D transcript as a novel potential therapy target.

Draft Genome Sequence of Bacillus thuringiensis Strain UNMSM10RA, Isolated from Potato Crop Soil in Peru.

The 5.5-Mb genome sequence of Bacillus thuringiensis strain UNMSM10RA, isolated from potato crop soil, is reported in this study. The strain UNMSM10RA contains 5,347 protein-coding sequences, 105 tRNA genes, 15 rRNA genes, and 5 noncoding RNA (ncRNA) genes, with an average G+C content of 35.1%.

Regulatory context drives conservation of glycine riboswitch aptamers.

In comparison to protein coding sequences, the impact of mutation and natural selection on the sequence and function of non-coding (ncRNA) genes is not well understood. Many ncRNA genes are narrowly distributed to only a few organisms, and appear to be rapidly evolving. Compared to protein coding sequences, there are many challenges associated with assessment of ncRNAs that are not well addressed by conventional phylogenetic approaches, including: short sequence length, lack of primary sequence conservation, and the importance of secondary structure for biological function. Riboswitches are structured ncRNAs that directly interact with small molecules to regulate gene expression in bacteria. They typically consist of a ligand-binding domain (aptamer) whose folding changes drive changes in gene expression. The glycine riboswitch is among the most well-studied due to the widespread occurrence of a tandem aptamer arrangement (tandem), wherein two homologous aptamers interact with glycine and each other to regulate gene expression. However, a significant proportion of glycine riboswitches are comprised of single aptamers (singleton). Here we use graph clustering to circumvent the limitations of traditional phylogenetic analysis when studying the relationship between the tandem and singleton glycine aptamers. Graph clustering enables a broader range of pairwise comparison measures to be used to assess aptamer similarity. Using this approach, we show that one aptamer of the tandem glycine riboswitch pair is typically much more highly conserved, and that which aptamer is conserved depends on the regulated gene. Furthermore, our analysis also reveals that singleton aptamers are more similar to either the first or second tandem aptamer, again based on the regulated gene. Taken together, our findings suggest that tandem glycine riboswitches degrade into functional singletons, with the regulated gene(s) dictating which glycine-binding aptamer is conserved.

EPD in 2020: enhanced data visualization and extension to ncRNA promoters.

The Eukaryotic Promoter Database (EPD), available online at https://epd.epfl.ch, provides accurate transcription start site (TSS) information for promoters of 15 model organisms plus corresponding functional genomics data that can be viewed in a genome browser, queried or analyzed via web interfaces, or exported in standard formats (FASTA, BED, CSV) for subsequent analysis with other tools. Recent work has focused on the improvement of the EPD promoter viewers, which use the UCSC Genome Browser as visualization platform. Thousands of high-resolution tracks for CAGE, ChIP-seq and similar data have been generated and organized into public track hubs. Customized, reproducible promoter views, combining EPD-supplied tracks with native UCSC Genome Browser tracks, can be accessed from the organism summary pages or from individual promoter entries. Moreover, thanks to recent improvements and stabilization of ncRNA gene catalogs, we were able to release promoter collections for certain classes of ncRNAs from human and mouse. Furthermore, we developed automatic computational protocols to assign orphan TSS peaks to downstream genes based on paired-end (RAMPAGE) TSS mapping data, which enabled us to add nearly 9000 new entries to the human promoter collection. Since our last article in this journal, EPD was extended to five more model organisms: rhesus monkey, rat, dog, chicken and Plasmodium falciparum.

Genome Sequence Announcement of Bacillus paranthracis Strain ICIS-279, Isolated from Human Intestine.

This report describes the genome sequence of Bacillus paranthracis strain ICIS-279, isolated from human feces. It demonstrates a tumor necrosis factor alpha (TNF-α) inhibitory activity up to 0.1 ng/ml. The genome size is 5,180,499 bp, with a G+C content of 35.4%. Annotation revealed 5,168 coding sequences, including 5,168 proteins and 43 rRNA, 102 tRNA, and 5 noncoding RNA (ncRNA) genes.

RNA therapeutics: Identification of novel targets leading to drug discovery.

The established concept that RNA works only for protein synthesis has been changed over the past few decades and shifted towards therapeutic purposes. Almost 98% of mammalian genome is transcribed into nonprotein coding RNA termed as noncoding RNA (ncRNA) which plays regulatory role in molecular and cellular functions as controlling gene expression. These ncRNAs are classified as long noncoding RNA (lncRNA), short noncoding RNA (sncRNA), and translational/structural RNA which possess diverse functions. These ncRNAs regulate expression of normal gene and modulate disease development and progression. The characterization of ncRNA genes and their mechanisms can aid in disease diagnosis, examining its development and direct specific therapies in different disease treatments. Due to their unique modes of action, they are designated as novel class of targets leading to drug discovery. The modulation in these ncRNAs can enhance therapeutic treatments against different diseases by targeting mRNA for its cleavage via antisense olionucleotides (ASOs)/DNA duplex, RNA alternative splicing/editing, chromatin modification, transcriptional/translational interference, RNA masking, small interfering RNA/microRNA-based gene silencing and by inducing immunity via RNA-based vaccination. Here in this review, we tried to summarize the emerging fields of ncRNA, their role in different diseases, their modes of action, and their potential in target identification and therapeutic drug development.