Oncogenic Roles of Small Nucleolar RNA Host Gene 7 (SNHG7) Long Noncoding RNA in Human Cancers and Potentials

Long noncoding RNAs (lncRNAs) are a class of noncoding transcripts characterized with more than 200 nucleotides of length. Unlike their names, some short open reading frames are recognized for them encoding small proteins. LncRNAs are found to play regulatory roles in essential cellular processes such as cell growth and apoptosis. Therefore, an increasing number of lncRNAs are identified with dysregulation in a wide variety of human cancers. SNHG7 is an lncRNA with upregulation in cancer cells and tissues. It is frequently reported with potency of promoting malignant cell behaviors in vitro and in vivo. Like oncogenic/tumor suppressor lncRNAs, SNHG7 is found to exert its tumorigenic functions through interaction with other biological substances. These include sponging target miRNAs (various numbers are identified), regulation of several signaling pathways, transcription factors, and effector proteins. Importantly, clinical studies demonstrate association between high SNHG7 expression and clinicopathological features in cancerous patients, worse prognosis, and enhanced chemoresistance. In this review, we summarize recent studies in three eras of cell, animal, and human experiments to bold the prognostic, diagnostic, and therapeutic potentials.

An endogenous retrovirus presumed to have been endogenized or relocated recently in a marsupial, the red-necked wallaby

An albino infant wallaby was born to a mother with the wild-type body color. PCR and sequencing analyses of <i>TYR</i> (encoding tyrosinase, which is essential for melanin biosynthesis) of this albino wallaby revealed a 7.1-kb-long DNA fragment inserted in the first exon. Because the fragment carried long terminal repeats, we assumed it to be a copy of an endogenous retrovirus, which we named <i>walb</i>. We cloned other <i>walb</i> copies residing in the genomes of this species and another wallaby species. The copies exhibited length variation, and the longest copy (>8.0 kb) contained open reading frames whose deduced amino acid sequences were well aligned with those of <i>gag</i>, <i>pol</i>, and <i>env</i> of retroviruses. It is not known through which of the following likely processes the walb copy was inserted into <i>TYR</i>: endogenization (infection of a germline cell by an exogenous virus), reinfection (infection by a virus produced from a previously endogenized provirus), or retrotransposition (intracellular relocation of a provirus). In any case, the insertion into <i>TYR</i> is considered to have been a recent event on an evolutionary timescale because albino mutant alleles generally do not persist for long because of their deleterious effects in wild circumstances.

Occurrence of Grapevine Leafroll-Associated Virus-3 (GLRaV-3), Complete Nucleotide Sequence and Cultivar Susceptibility to a GLRaV-3 Isolate from Shaanxi Province of China

Grapevine (Vitis spp.) is globally one of the most economically important fruit crops. China is the largest grapevine-growing country of the world and Shaanxi province is one of the major grapevine-growing provinces in the country. A survey of GLRaV-3 found it widespread, with 57–100% infection frequencies, in both wine and table grapevine cultivars of three grapevine-growing regions of Shaanxi province. The virus infection frequencies varied with cultivars and regions. In order to obtain the full genomic length of a new GLRaV-3 isolate, GLRaV-3-Sau (accession number MK988555), was sequenced. This isolate has a genome of 18026 nucleotides, and 14 open reading frames (ORFs). The full-genome of the isolate GLRaV-3-Sau shared 85.88% nucleotide identity to GLRaV-3-LN, another isolate found in China. Coat protein (CP) genes of GLRaV-3 isolates were identical (99%) to the Vitis vinifera isolate (accession number HQ185608.1) from the USA. Immunohistochemistry for virus localization found that distribution patterns were similar in red-berried cultivar ‘Cabernet Sauvignon’ and white-berried cultivar ‘Chardonnay’, and GLRaV-3 is restricted in phloem tissue of vascular bundles. Virus transmission by micrografting found virus transmission efficiency was higher in ‘Chardonnay’ and ‘Thompson Seedless’ than in ‘Hunan-1’, indicating that ‘Hunan-1’ was less sensitive to GLRaV-3. As far as we know, these are the most comprehensive comparisons on the genome and CP genes of GLRaV-3 worldwide and the first to have found that the grapevine ‘Hunan-1’ is less susceptible to GLRaV-3.

Complete Genome Sequence of Curtobacterium sp. Strain TXMA1, Isolated from a Grapevine in Texas, USA

The genome of Curtobacterium sp. strain TXMA1, isolated from a grapevine in Texas showing leaf marginal necrosis symptoms, was sequenced. The TXMA1 genome has a 3,454,876-bp, circular chromosome with a GC content of 71.74%, 3,213 open reading frames (ORFs), 47 tRNAs, and 4 complete rRNA operons (5S, 16S, and 23S).

Genomic Characterization of a Novel Freshwater Cyanophage Reveals a New Lineage of Cyanopodovirus

Cyanobacteria are one of the dominant autotrophs in tropical freshwater communities, yet phages infecting them remain poorly characterized. Here we present the characterization of cyanophage S-SRP02, isolated from a tropical freshwater lake in Singapore, which infects Synechococcus sp. Strain SR-C1 isolated from the same lake. S-SRP02 represents a new evolutionary lineage of cyanophage. Out of 47 open reading frames (ORFs), only 20 ORFs share homology with genes encoding proteins of known function. There is lack of auxiliary metabolic genes which was commonly found as core genes in marine cyanopodoviruses. S-SRP02 also harbors unique structural genes highly divergent from other cultured phages. Phylogenetic analysis and viral proteomic tree further demonstrate the divergence of S-SRP02 from other sequenced phage isolates. Nonetheless, S-SRP02 shares synteny with phage genes of uncultured phages obtained from the Mediterranean Sea deep chlorophyll maximum fosmids, indicating the ecological importance of S-SRP02 and its related viruses. This is further supported by metagenomic mapping of environmental viral metagenomic reads onto the S-SRP02 genome.

Identification and Fine Mapping of the Recessive Gene BK-5, Which Affects Cell Wall Biosynthesis and Plant Brittleness in Maize

The cellulose of the plant cell wall indirectly affects the cell shape and straw stiffness of the plant. Here, the novel brittleness mutant brittle stalk-5 (bk-5) of the maize inbred line RP125 was characterized. We found that the mutant displayed brittleness of the stalk and even the whole plant, and that the brittleness phenotype existed during the whole growth period from germination to senescence. The compressive strength was reduced, the cell wall was thinner, and the cellulose content was decreased compared to that of the wild type. Genetic analysis and map-based cloning indicated that bk-5 was controlled by a single recessive nuclear gene and that it was located in a 90.2-Kb region on chromosome 3 that covers three open reading frames (ORFs). Sequence analysis revealed a single non-synonymous missense mutation, T-to-A, in the last exon of Zm00001d043477 (B73: version 4, named BK-5) that caused the 951th amino acid to go from leucine to histidine. BK-5 encodes a cellulose synthase catalytic subunit (CesA), which is involved with cellulose synthesis. We found that BK-5 was constitutively expressed in all tissues of the germinating stage and silking stage, and highly expressed in the leaf, auricula, and root of the silking stage and the 2-cm root and bud of the germinating stage. We found that BK-5 mainly localized to the Golgi apparatus, suggesting that the protein might move to the plasma membrane with the aid of Golgi in maize. According to RNA-seq data, bk-5 had more downregulated genes than upregulated genes, and many of the downregulated genes were enzymes and transcription factors related to cellulose, hemicellulose, and lignin biosynthesis of the secondary cell wall. The other differentially expressed genes were related to metabolic and cellular processes, and were significantly enriched in hormone signal transduction, starch and sucrose metabolism, and the plant–pathogen interaction pathway. Taken together, we propose that the mutation of gene BK-5 causes the brittle stalk phenotype and provides important insights into the regulatory mechanism of cellulose biosynthesis and cell wall development in maize.

Translational buffering by ribosome stalling in upstream open reading frames

Upstream open reading frames (uORFs) are present in over half of all human mRNAs. uORFs can potently regulate the translation of downstream open reading frames by several mechanisms: siphoning away scanning ribosomes, regulating re-initiation, and allowing interactions between scanning and elongating ribosomes. However, the consequences of these different mechanisms for the regulation of protein expression remain incompletely understood. Here, we performed systematic measurements on the uORF-containing 5′ UTR of the cytomegaloviral UL4 mRNA to test alternative models of uORF-mediated regulation in human cells. We find that a terminal diproline-dependent elongating ribosome stall in the UL4 uORF prevents decreases in main ORF translation when ribosome loading onto the mRNA is reduced. This uORF-mediated buffering is insensitive to the location of the ribosome stall along the uORF. Computational kinetic modeling based on our measurements suggests that scanning ribosomes dissociate rather than queue when they collide with stalled elongating ribosomes within the UL4 uORF. We identify several human uORFs that repress main ORF translation via a similar terminal diproline motif. We propose that ribosome stalls in uORFs provide a general mechanism for buffering against reductions in main ORF translation during stress and developmental transitions.

Integrative profiling of Epstein–Barr virus transcriptome using a multiplatform approach

Background Epstein–Barr virus (EBV) is an important human pathogenic gammaherpesvirus with carcinogenic potential. The EBV transcriptome has previously been analyzed using both Illumina-based short read-sequencing and Pacific Biosciences RS II-based long-read sequencing technologies. Since the various sequencing methods have distinct strengths and limitations, the use of multiplatform approaches have proven to be valuable. The aim of this study is to provide a more complete picture on the transcriptomic architecture of EBV. Methods In this work, we apply the Oxford Nanopore Technologies MinION (long-read sequencing) platform for the generation of novel transcriptomic data, and integrate these with other’s data generated by another LRS approach, Pacific BioSciences RSII sequencing and Illumina CAGE-Seq and Poly(A)-Seq approaches. Both amplified and non-amplified cDNA sequencings were applied for the generation of sequencing reads, including both oligo-d(T) and random oligonucleotide-primed reverse transcription. EBV transcripts are identified and annotated using the LoRTIA software suite developed in our laboratory. Results This study detected novel genes embedded into longer host genes containing 5′-truncated in-frame open reading frames, which potentially encode N-terminally truncated proteins. We also detected a number of novel non-coding RNAs and transcript length isoforms encoded by the same genes but differing in their start and/or end sites. This study also reports the discovery of novel splice isoforms, many of which may represent altered coding potential, and of novel replication-origin-associated transcripts. Additionally, novel mono- and multigenic transcripts were identified. An intricate meshwork of transcriptional overlaps was revealed. Conclusions An integrative approach applying multi-technique sequencing technologies is suitable for reliable identification of complex transcriptomes because each techniques has different advantages and limitations, and the they can be used for the validation of the results obtained by a particular approach.

Evaluating Expression of the STAG1 Gene as a Potential Breast Cancer Biomarker

STAG proteins, which are part of the cohesin complex and encoded by the STAG genes, are known as Irr1/Scc3 in yeast and as SA/STAG/stromalin in mammals. There are more variants as there are alternate splice sites, maybe three open reading frames (ORFs) code for three main proteins, including: SA1 (STAG1), SA2 (STAG2) and SA3 (STAG3). The cohesin protein complex has various essential roles in eukaryotic cell biology. This study compared the expression of the STAG1 gene in four different breast cancer cell lines, including: MCF-7, T-47D, MDA-MB-468, and MDA-MB-231 and normal breast tissue. RNA was extracted from these cell lines and mRNA was converted to cDNA, and then expression of the STAG1 gene was quantified by three sets of specific primer pairs using Real Time-quantitative PCR (RT-qPCR). The findings show significantly different over-expression of STAG1 in these cancer cell lines in comparison with the normal tissue, and the cell lines were different in their expression levels. In conclusion, the STAG1 gene can be postulated as a candidate breast cancer biomarker that needs to be further evaluated in breast tumor biopsies.