Analysis of intronless genes involved in oscillation and differentiation

The genomes of higher eukaryotes are replete with intron-containing genes. Transcription of these genes produces precursor mRNAs containing intervening sequences, which are subsequently removed and the exons spliced together to form the mature mRNA. However, a small proportion of eukaryotic protein-coding genes are intronless and therefore bypass post-transcriptional splicing events. Although a large proportion of intronless genes are known to code for certain types of proteins, their specific role in the genome of higher organism is perplexing. This research set out to elucidate the functions of intronless genes in humans by studying their involvement in the expression pattern of oscillatory gene that occurs in the pre-somitic mesoderm of developing embryo. Twenty-seven (27) human homologs of mouse oscillatory genes were analysed to determine the number of exons present in them using various bioinformatics databases. The result obtained identified two intronless genes –NRARP and ID1 – which are associated with the Notch signalling pathway of the segmentation clock. This represented 7.4% of the total oscillatory genes analysed. No intronless gene was found in the Wnt and FGF signalling pathways – two other pathways famous for oscillatory gene expression. The proteins encoded by the intronless genes are involved in several important biological processes including angiogenesis, cell cycle control and in the regulation of cellular senescence. Although oscillatory genes had fewer numbers of introns compared to the non-oscillatory genes, the intronless genes were not implicated in the regulation of the precise timing events of the segmentation clock. This result may also point to the fact that the rapid expression rate of the oscillatory genes in the PSM may favour the reduced intron length of the oscillatory genes.

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Sucl+ encodes a predicted 13-kilodalton protein that is essential for cell viability and is directly involved in the division cycle of Schizosaccharomyces pombe

Molecular and Cellular Biology ◽

10.1128/mcb.7.1.504-511.1987 ◽

1987 ◽

Vol 7 (1) ◽

pp. 504-511 ◽

Cited By ~ 2

Author(s):

J Hindley ◽

G Phear ◽

M Stein ◽

D Beach

Keyword(s):

Cell Division ◽

Schizosaccharomyces Pombe ◽

Cell Cycle Control ◽

Temperature Sensitive ◽

Base Pairs ◽

Direct Role ◽

Protein Coding ◽

Dna Fragment ◽

Rna Transcript ◽

Translational Product

Sucl+ was originally identified as a DNA sequence that, at high copy number, rescued Schizosaccharomyces pombe strains carrying certain temperature-sensitive alleles of the cdc2 cell cycle control gene. We determined the nucleotide sequence of a 1,083-base-pair Sucl+ DNA fragment and S1 mapped its 866-nucleotide RNA transcript. The protein-coding sequence of the gene is interrupted by two intervening sequences of 115 and 51 base pairs. The predicted translational product of the gene is a protein of 13 kilodaltons. A chromosomal gene disruption of Sucl+ was constructed in a diploid S. pombe strain. Germinating spores carrying a null allele of the gene were capable of very limited cell division, following which many cells became highly elongated. The Sucl+ gene was also strongly overexpressed under the control of a heterologous S. pombe promoter. Overexpression of Sucl+ is not lethal but causes a division delay such that cells are approximately twice the normal length at division. These data suggest that Sucl+ encodes a protein which plays a direct role in the cell division cycle of S. pombe.

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CircHIPK3 dysregulation of the miR-30c/DLL4 axis is essential for KSHV lytic replication

10.1101/2021.10.07.463491 ◽

2021 ◽

Author(s):

Katherine L Harper ◽

Timothy J Mottram ◽

Chinedu A Arene ◽

Becky Foster ◽

Molly R Patterson ◽

...

Keyword(s):

Gene Expression ◽

B Cells ◽

Regulatory Network ◽

Regulatory Networks ◽

Cell Cycle Control ◽

Lytic Replication ◽

Protein Coding ◽

Non Coding Rna ◽

Novel Host ◽

Cellular Pathways

Non coding RNA (ncRNA) regulatory networks are emerging as critical regulators of gene expression. These intricate networks of ncRNA-ncRNA interactions modulate multiple cellular pathways and impact the development and progression of multiple diseases. Herpesviruses, including Kaposi's sarcoma-associated herpesvirus, are adept at utilising ncRNAs, encoding their own as well as dysregulating host ncRNAs to modulate virus gene expression and the host response to infection. Research has mainly focused on unidirectional ncRNA-mediated regulation of target protein-coding transcripts; however, we have identified a novel host ncRNA regulatory network essential for KSHV lytic replication in B cells. KSHV-mediated upregulation of the host cell circRNA, circHIPK3, is a key component of this network, functioning as a competing endogenous RNA of miR-30c, leading to increased levels of the miR-30c target, DLL4. Dysregulation of this network highlights a novel mechanism of cell cycle control during KSHV lytic replication in B cells. Importantly, disruption at any point within this novel ncRNA regulatory network has a detrimental effect on KSHV lytic replication, highlighting the essential nature of this network and potential for therapeutic intervention.

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Functional profiling of long intergenic non-coding RNAs in fission yeast

eLife ◽

10.7554/elife.76000 ◽

2022 ◽

Vol 11 ◽

Author(s):

Maria Rodriguez-Lopez ◽

Shajahan Anver ◽

Cristina Cotobal ◽

Stephan Kamrad ◽

Michal Malecki ◽

...

Keyword(s):

High Throughput ◽

Cell Cycle Control ◽

Colony Growth ◽

Cellular Functions ◽

Protein Coding ◽

Functional Profiling ◽

Functional Inference ◽

Functional Context ◽

Non Coding Rnas ◽

Eukaryotic Genomes

Eukaryotic genomes express numerous long intergenic non-coding RNAs (lincRNAs) that do not overlap any coding genes. Some lincRNAs function in various aspects of gene regulation, but it is not clear in general to what extent lincRNAs contribute to the information flow from genotype to phenotype. To explore this question, we systematically analysed cellular roles of lincRNAs in Schizosaccharomyces pombe. Using seamless CRISPR/Cas9-based genome editing, we deleted 141 lincRNA genes to broadly phenotype these mutants, together with 238 diverse coding-gene mutants for functional context. We applied high-throughput colony-based assays to determine mutant growth and viability in benign conditions and in response to 145 different nutrient, drug, and stress conditions. These analyses uncovered phenotypes for 47.5% of the lincRNAs and 96% of the protein-coding genes. For 110 lincRNA mutants, we also performed high-throughput microscopy and flow cytometry assays, linking 37% of these lincRNAs with cell-size and/or cell-cycle control. With all assays combined, we detected phenotypes for 84 (59.6%) of all lincRNA deletion mutants tested. For complementary functional inference, we analysed colony growth of strains ectopically overexpressing 113 lincRNA genes under 47 different conditions. Of these overexpression strains, 102 (90.3%) showed altered growth under certain conditions. Clustering analyses provided further functional clues and relationships for some of the lincRNAs. These rich phenomics datasets associate lincRNA mutants with hundreds of phenotypes, indicating that most of the lincRNAs analysed exert cellular functions in specific environmental or physiological contexts. This study provides groundwork to further dissect the roles of these lincRNAs in the relevant conditions.

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Cell Cycle Control by Nuclear Sequestration ofCDC20andCDH1mRNA in Plant Stem Cells

10.1101/198978 ◽

2017 ◽

Author(s):

Weibing Yang ◽

Raymond Wightman ◽

Elliot M. Meyerowitz

Keyword(s):

Cell Cycle ◽

Nuclear Localization ◽

Cell Cycle Control ◽

Protein Translation ◽

Messenger Rnas ◽

Protein Coding ◽

Rna Molecules ◽

Nuclear Envelope Breakdown ◽

And Function ◽

Necessary And Sufficient

AbstractIn eukaryotic cells, most RNA molecules are exported into the cytoplasm after being transcribed in the nucleus. Long noncoding RNAs (lncRNAs) have been found to reside and function primarily inside the nucleus, but nuclear localization of protein-coding messenger RNAs (mRNAs) has been considered rare in both animals and plants. Here we show that two mRNAs, transcribed from theCDC20andCCS52B(plant orthologue ofCDH1) genes, are specifically sequestered inside the nucleus during the cell cycle. CDC20 and CDH1 both function as coactivators of the anaphase-promoting complex or cyclosome (APC/C) E3 ligase to trigger cyclin B (C YCB) destruction. In theArabidopsis thalianashoot apical meristem (SAM), we findCDC20andCCS52Bare co-expressed withCYCBsin mitotic cells.CYCBtranscripts can be exported and translated, whereasCDC20andCCS52BmRNAs are strictly confined to the nucleus at prophase and the cognate proteins are not translated until the redistribution of the mRNAs to the cytoplasm after nuclear envelope breakdown (NEBD) at prometaphase. The 5’ untranslated region (UTR) is necessary and sufficient forCDC20mRNA nuclear localization as well as protein translation. Mitotic enrichment ofCDC20andCCS52Btranscripts enables the timely and rapid activation of APC/C, while their nuclear sequestration at prophase appears to protect cyclins from precocious degradation.

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Integrated Transcriptomics Explored the Cancer-Promoting Genes CDKN3 in Esophageal Squamous Cell Cancer

10.21203/rs.3.rs-127861/v1 ◽

2020 ◽

Author(s):

Wanpeng Wang ◽

Kai Liao ◽

HaoChun Guo ◽

Suqin Zhou ◽

Ran Yu ◽

...

Keyword(s):

Clinical Significance ◽

Expression Patterns ◽

Cell Cancer ◽

Expression Level ◽

Clinical Staging ◽

P Value ◽

Tissue Samples ◽

Protein Coding ◽

Seed Gene ◽

Expression Rate

Abstract Background and objectives: The aims of the present study were to explore the critical genes that related to development of ESCC by integrated transcriptomics and investigate the clinical significance by experimental validation. Methods: The datasets of protein-coding genes expression which involved in ESCC were downloaded from GEO database. The "Robustrankaggreg" package was used for data integration, and the different expression genes (DEGs) were identified based the cut-off criteria as follows: adjust p-value < 0.05, |Log2 fold change (FC)| ≥ 1.5; The protein expression of seed gene in 184 cases of primary ESCC were detected by immunohistochemistry; The relationship between the expression level of seed genes and clinical significance were analyze. Results: A total of 244 DEGs were identified by comparing gene expression patterns between ESCC patients and the controls based on integrating dataset of GSE77861, GSE77861, GSE100942, GSE26886, GSE17351, GSE38129, GSE33426, GSE20347 and GSE23400; The CDKN3 were identified the seed gene of top cluster by use of PPI network and plug-in MCODE; The level of CDKN3 mRNA was significantly increased in ESCC patients compared to controls; The positive expression rate of CDKN3 protein in ESCC tissue samples was 32.0% and 61.4% in control, respectively, differences were statistically significant; There was significant correlation between the expression level of CDKN3 and lymph node metastasis or clinical staging of ESCC patients. Conclusion: Integrated transcriptomics is an efficient approach to system biology. By this procedure, our study improved the understanding of the transcriptome status of ESCC.

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Sucl+ encodes a predicted 13-kilodalton protein that is essential for cell viability and is directly involved in the division cycle of Schizosaccharomyces pombe.

Molecular and Cellular Biology ◽

10.1128/mcb.7.1.504 ◽

1987 ◽

Vol 7 (1) ◽

pp. 504-511 ◽

Cited By ~ 98

Author(s):

J Hindley ◽

G Phear ◽

M Stein ◽

D Beach

Keyword(s):

Cell Division ◽

Schizosaccharomyces Pombe ◽

Cell Cycle Control ◽

Temperature Sensitive ◽

Base Pairs ◽

Direct Role ◽

Protein Coding ◽

Dna Fragment ◽

Rna Transcript ◽

Translational Product

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The Roles and Evolutionary Patterns of Intronless Genes in Deuterostomes

Comparative and Functional Genomics ◽

10.1155/2011/680673 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 13

Author(s):

Ming Zou ◽

Baocheng Guo ◽

Shunping He

Keyword(s):

Gene Ontology ◽

Common Ancestor ◽

Evolutionary Patterns ◽

Intronless Gene ◽

Basic Part ◽

Sea Squirt ◽

Intronless Genes ◽

Eukaryotic Genes ◽

Primitive Species ◽

The Common

Genes without introns are a characteristic feature of prokaryotes, but there are still a number of intronless genes in eukaryotes. To study these eukaryotic genes that have prokaryotic architecture could help to understand the evolutionary patterns of related genes and genomes. Our analyses revealed a number of intronless genes that reside in 6 deuterostomes (sea urchin, sea squirt, zebrafish, chicken, platypus, and human). We also determined the conservation for each intronless gene in archaea, bacteria, fungi, plants, metazoans, and other eukaryotes. Proportions of intronless genes that are inherited from the common ancestor of archaea, bacteria, and eukaryotes in these species were consistent with their phylogenetic positions, with more proportions of ancient intronless genes residing in more primitive species. In these species, intronless genes belong to different cellular roles and gene ontology (GO) categories, and some of these functions are very basic. Part of intronless genes is derived from other intronless genes or multiexon genes in each species. In conclusion, we showed that a varying number and proportion of intronless genes reside in these 6 deuterostomes, and some of them function importantly. These genes are good candidates for subsequent functional and evolutionary analyses specifically.

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Beta-hydroxybutyrate infusion identifies acutely differentially expressed genes related to metabolism and reproduction in the hypothalamus and pituitary of castrated male sheep

Physiological Genomics ◽

10.1152/physiolgenomics.00104.2017 ◽

2018 ◽

Vol 50 (6) ◽

pp. 468-477

Author(s):

Emily R. Cope ◽

Brynn H. Voy ◽

Brian K. Whitlock ◽

Meg Staton ◽

Thomas Lane ◽

...

Keyword(s):

Bos Taurus ◽

Cell Cycle Control ◽

Ovis Aries ◽

Functional Enrichment ◽

Differentially Expressed ◽

Protein Coding ◽

Altered Expression ◽

Expression Of Genes ◽

Beta Hydroxybutyrate ◽

Male Sheep

To identify molecular pathways that couple metabolic imbalances and reproduction, we randomly assigned 10 castrated male sheep to be centrally injected into the lateral ventricle through intracerebroventricular cannulas with 1 ml of β-hydroxybutyric acid sodium salt solution (BHB; 12,800 µmol/l) or saline solution (CON; 0.9% NaCl). Approximately 2 h postinjection, sheep were humanely euthanized, and hypothalamus and pituitary tissues were harvested for transcriptome characterization by RNA sequencing. RNA was extracted from the hypothalamus and pituitary and sequenced at a high depth (hypothalamus: 468,912,732 reads; pituitary: 515,106,092 reads) with the Illumina Hi-Seq 2500 platform and aligned to Bos taurus and Ovis aries genomes. Of the total raw reads, 87% (hypothalamus) and 90.5% (pituitary) mapped to the reference O. aries genome. Within these read sets, ~56% in hypothalamus and 69% in pituitary mapped to either known or putative protein coding genes. Fragments per kilobase of transcripts per million normalized counts were averaged and ranked to identify the transcript expression level. Gene Ontology analysis (DAVID Bioinformatics Resources) was utilized to identify biological process functions related to genes shared between tissues, as well as functional categories with tissue-specific enrichment. Between CON- and BHB-treated sheep, 11 and 44 genes were differentially expressed (adj. P < 0.05) within the pituitary and hypothalamus, respectively. Functional enrichment analyses revealed BHB altered expression of genes in pathways related to stimulus perception, inflammation, and cell cycle control. The set of genes altered by BHB creates a foundation from which to identify the signaling pathways that impact reproduction during metabolic imbalances.

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