scholarly journals Dynamics and modulation of the human snoRNome

2021 ◽  
Author(s):  
Étienne Fafard-Couture ◽  
Danny Bergeron ◽  
Sonia Couture ◽  
Sherif Abou Elela ◽  
Michelle S Scott
Keyword(s):  
Expression Patterns ◽  
Housekeeping Genes ◽  
Host Gene ◽  
Rna Modification ◽  
Human Tissues ◽  
Healthy Human ◽  
Protein Coding ◽  
Conservation Level ◽  
Nucleolar Rnas ◽  
Host Genes

AbstractBackgroundSmall nucleolar RNAs (snoRNAs) are mid-size non-coding RNAs required for ribosomal RNA modification, implying a ubiquitous tissue distribution linked to ribosome synthesis. However, increasing numbers of studies identify extra-ribosomal roles of snoRNAs in modulating gene expression, suggesting more complex snoRNA expression patterns. Therefore, there is a great need for mapping the snoRNome in different human tissues as the blueprint for snoRNA functions.ResultsWe used a low structure bias RNA-Seq approach to accurately quantify snoRNAs and compare them to the entire transcriptome in seven healthy human tissues (breast, ovary, prostate, testis, skeletal muscle, liver and brain). We identified 475 expressed snoRNAs categorized in two abundance classes that differ significantly in their function, conservation level and correlation with their host gene: 390 snoRNAs are uniformly expressed and 85 are enriched in the brain or reproductive tissues. Most tissue-enriched snoRNAs are embedded in lncRNAs and display strong correlation of abundance with them, whereas uniformly expressed snoRNAs are mostly embedded in protein-coding host genes and are mainly non- or anticorrelated with them. 59% of the non-correlated or anticorrelated protein-coding host gene/snoRNA pairs feature dual-initiation promoters, as opposed to only 16% of the correlated non-coding host gene/snoRNA pairs.ConclusionsOur results demonstrate that snoRNAs are not a single homogeneous group of housekeeping genes but include highly regulated tissue-enriched RNAs. Indeed, our work indicates that the architecture of snoRNA host genes varies to uncouple the host and snoRNA expressions in order to meet the different snoRNA abundance levels and functional needs of human tissues.

scholarly journals Annotation of snoRNA abundance across human tissues reveals complex snoRNA-host gene relationships

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Étienne Fafard-Couture ◽  
Danny Bergeron ◽  
Sonia Couture ◽  
Sherif Abou-Elela ◽  
Michelle S. Scott
Keyword(s):  
Housekeeping Genes ◽  
Host Gene ◽  
Rna Modification ◽  
Human Tissues ◽  
Rna Seq ◽  
Healthy Human ◽  
Protein Coding ◽  
Conservation Level ◽  
Nucleolar Rnas ◽  
Host Genes

Abstract Background Small nucleolar RNAs (snoRNAs) are mid-size non-coding RNAs required for ribosomal RNA modification, implying a ubiquitous tissue distribution linked to ribosome synthesis. However, increasing numbers of studies identify extra-ribosomal roles of snoRNAs in modulating gene expression, suggesting more complex snoRNA abundance patterns. Therefore, there is a great need for mapping the snoRNome in different human tissues as the blueprint for snoRNA functions. Results We used a low structure bias RNA-Seq approach to accurately quantify snoRNAs and compare them to the entire transcriptome in seven healthy human tissues (breast, ovary, prostate, testis, skeletal muscle, liver, and brain). We identify 475 expressed snoRNAs categorized in two abundance classes that differ significantly in their function, conservation level, and correlation with their host gene: 390 snoRNAs are uniformly expressed and 85 are enriched in the brain or reproductive tissues. Most tissue-enriched snoRNAs are embedded in lncRNAs and display strong correlation of abundance with them, whereas uniformly expressed snoRNAs are mostly embedded in protein-coding host genes and are mainly non- or anticorrelated with them. Fifty-nine percent of the non-correlated or anticorrelated protein-coding host gene/snoRNA pairs feature dual-initiation promoters, compared to only 16% of the correlated non-coding host gene/snoRNA pairs. Conclusions Our results demonstrate that snoRNAs are not a single homogeneous group of housekeeping genes but include highly regulated tissue-enriched RNAs. Indeed, our work indicates that the architecture of snoRNA host genes varies to uncouple the host and snoRNA expressions in order to meet the different snoRNA abundance levels and functional needs of human tissues.

scholarly journals Are spliced ncRNA host genes distinct classes of lncRNAs?

2020 ◽  
Vol 139 (4) ◽  
pp. 349-359
Author(s):  
Rituparno Sen ◽  
Jörg Fallmann ◽  
Maria Emília M. T. Walter ◽  
Peter F. Stadler
Keyword(s):  
Gene Function ◽  
Negative Answer ◽  
Positive Answer ◽  
Host Gene ◽  
Small Nucleolar Rnas ◽  
Biological Functions ◽  
Protein Coding ◽  
Non Coding Rnas ◽  
Nucleolar Rnas ◽  
Host Genes

AbstractMany small nucleolar RNAs and many of the hairpin precursors of miRNAs are processed from long non-protein-coding host genes. In contrast to their highly conserved and heavily structured payload, the host genes feature poorly conserved sequences. Nevertheless, there is mounting evidence that the host genes have biological functions beyond their primary task of carrying a ncRNA as payload. So far, no connections between the function of the host genes and the function of their payloads have been reported. Here we investigate whether there is evidence for an association of host gene function or mechanisms with the type of payload. To assess this hypothesis we test whether the miRNA host genes (MIRHGs), snoRNA host genes (SNHGs), and other lncRNA host genes can be distinguished based on sequence and/or structure features unrelated to their payload. A positive answer would imply a functional and mechanistic correlation between host genes and their payload, provided the classification does not depend on the presence and type of the payload. A negative answer would indicate that to the extent that secondary functions are acquired, they are not strongly constrained by the prior, primary function of the payload. We find that the three classes can be distinguished reliably when the classifier is allowed to extract features from the payloads. They become virtually indistinguishable, however, as soon as only sequence and structure of parts of the host gene distal from the snoRNAs or miRNA payload is used for classification. This indicates that the functions of MIRHGs and SNHGs are largely independent of the functions of their payloads. Furthermore, there is no evidence that the MIRHGs and SNHGs form coherent classes of long non-coding RNAs distinguished by features other than their payloads.

scholarly journals Separated Siamese Twins: Intronic Small Nucleolar RNAs and Matched Host Genes May be Altered in Conjunction or Separately in Multiple Cancer Types

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 387 ◽  
Author(s):  
Marianna Penzo ◽  
Rosanna Clima ◽  
Davide Trerè ◽  
Lorenzo Montanaro
Keyword(s):  
Copy Number ◽  
Host Gene ◽  
The Cancer Genome Atlas ◽  
Cancer Development ◽  
Rna Modification ◽  
Small Nucleolar Rnas ◽  
Multiple Cancer ◽  
Cancer Types ◽  
Nucleolar Rnas ◽  
Host Genes

Small nucleolar RNAs (snoRNAs) are non-coding RNAs involved in RNA modification and processing. Approximately half of the so far identified snoRNA genes map within the intronic regions of host genes, and their expression, as well as the expression of their host genes, is dependent on transcript splicing and maturation. Growing evidence indicates that mutations and/or deregulations that affect snoRNAs, as well as host genes, play a significant role in oncogenesis. Among the possible factors underlying snoRNA/host gene expression deregulation is copy number alteration (CNA). We analyzed the data available in The Cancer Genome Atlas database, relative to CNA and expression of 295 snoRNA/host gene couples in 10 cancer types, to understand whether the genetic or expression alteration of snoRNAs and their matched host genes would have overlapping trends. Our results show that, counterintuitively, copy number and expression alterations of snoRNAs and matched host genes are not necessarily coupled. In addition, some snoRNA/host genes are mutated and overexpressed recurrently in multiple cancer types. Our findings suggest that the differential contribution to cancer development of both snoRNAs and host genes should always be considered, and that snoRNAs and their host genes may contribute to cancer development in conjunction or independently.

scholarly journals Supervised and Unsupervised Classification of lncRNA Subtypes

2020 ◽  
Author(s):  
Rituparno Sen ◽  
Jörg Fallmann ◽  
Maria Emília M. T. Walter ◽  
Peter F. Stadler
Keyword(s):  
Unsupervised Classification ◽  
Positive Answer ◽  
Host Gene ◽  
Small Nucleolar Rnas ◽  
Biological Functions ◽  
Protein Coding ◽  
Non Coding Rnas ◽  
Nucleolar Rnas ◽  
Host Genes

AbstractMany small nucleolar RNAs and many of the hairpin precursors of miRNAs are processed from long non-protein-coding (lncRNA) host genes. In contrast to their highly conserved and heavily structured payload, the host genes feature poorly conserved sequences. Nevertheless there is mounting evidence that the host genes have biological functions. No obvious connections between the function of the host genes and the function of their payloads have been reported. Here we inverstigate whether there is an association of host gene function or mechanisms with the type of payload. To assess this hypothesis we test whether the miRNA host genes (MIRHGs), snoRNA host genes (SNHGs), and other lncRNAs host genes can be distinguished based on sequence and structure features. A positive answer would imply a correlation between host genes and their payload. While the three classes can be distinguished reliably when the classifier is allowed to extract features from the payloads, this is no longer the case when only sequence and structure of parts of the host gene distal from the snoRNAs or miRNA payload is used for classification. Our data indicate that the functions of MIRHGs and SNHGs are largely independent of the functions of their payloads. Furthermore, there is no evidence that the MIRHGs and SNHGs form coherent classes of long non-coding RNAs distinguished by features other than their payloads.

scholarly journals Host Gene Regulation by Transposable Elements: The New, the Old and the Ugly

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1089 ◽  
Author(s):  
Rocio Enriquez-Gasca ◽  
Poppy A. Gould ◽  
Helen M. Rowe
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transposable Elements ◽  
Essential Gene ◽  
Expression Patterns ◽  
Genetic Material ◽  
Endogenous Retroviruses ◽  
Host Gene ◽  
New Genes ◽  
Host Genes

The human genome has been under selective pressure to evolve in response to emerging pathogens and other environmental challenges. Genome evolution includes the acquisition of new genes or new isoforms of genes and changes to gene expression patterns. One source of genome innovation is from transposable elements (TEs), which carry their own promoters, enhancers and open reading frames and can act as ‘controlling elements’ for our own genes. TEs include LINE-1 elements, which can retrotranspose intracellularly and endogenous retroviruses (ERVs) that represent remnants of past retroviral germline infections. Although once pathogens, ERVs also represent an enticing source of incoming genetic material that the host can then repurpose. ERVs and other TEs have coevolved with host genes for millions of years, which has allowed them to become embedded within essential gene expression programmes. Intriguingly, these host genes are often subject to the same epigenetic control mechanisms that evolved to combat the TEs that now regulate them. Here, we illustrate the breadth of host gene regulation through TEs by focusing on examples of young (The New), ancient (The Old), and disease-causing (The Ugly) TE integrants.

scholarly journals LINE-2 transposable elements are a source for functional human microRNAs and target sites

2017 ◽  
Author(s):  
Rebecca Petri ◽  
Per Ludvik Brattås ◽  
Yogita Sharma ◽  
Marie E Jönsson ◽  
Karolina Pircs ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Consensus Sequence ◽  
Housekeeping Genes ◽  
Small Rna Sequencing ◽  
Human Tissues ◽  
Human Brain Tissue ◽  
Protein Coding ◽  
Target Sites ◽  
Rna Immunoprecipitation ◽  
Low Levels

AbstractTransposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA Immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) elements, which entered the human genome around 100-300 million years ago. We found that L2-miRNAs derive from the 3’ end of the L2 consensus sequence and thus share very similar sequences, indicating that they could target transcripts with L2s in their 3’UTR. In line with this, we found that many protein-coding genes carry fragments of L2-derived sequences in their 3’UTR, which serve as target sites for L2-miRNAs. L2-miRNAs and targets were generally ubiquitously expressed at low levels in multiple human tissues, suggesting a role for this network in buffering transcriptional levels of housekeeping genes. Interestingly, we also found evidence that this network is perturbed in glioblastoma. In summary, our findings uncover a TE-based post-transcriptional network that shapes transcriptional regulation in human cells.

scholarly journals Intragenic MicroRNAs Autoregulate Their Host Genes in Both Direct and Indirect Ways—A Cross-Species Analysis

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 232 ◽  
Author(s):  
Maximilian Zeidler ◽  
Alexander Hüttenhofer ◽  
Michaela Kress ◽  
Kai K. Kummer
Keyword(s):  
Target Prediction ◽  
Gene Clusters ◽  
Host Gene ◽  
Gene Interactions ◽  
Protein Coding ◽  
Species Analysis ◽  
Recognition Elements ◽  
Autoregulatory Mechanism ◽  
Host Genes ◽  
Entire Gene

MicroRNAs (miRNAs) function as master switches for post-transcriptional gene expression. Their genes are either located in the extragenic space or within host genes, but these intragenic miRNA::host gene interactions are largely enigmatic. The aim of this study was to investigate the location and co-regulation of all to date available miRNA sequences and their host genes in an unbiased computational approach. The majority of miRNAs were located within intronic regions of protein-coding and non-coding genes. These intragenic miRNAs exhibited both increased target probability as well as higher target prediction scores as compared to a model of randomly permutated genes. This was associated with a higher number of miRNA recognition elements for the hosted miRNAs within their host genes. In addition, strong indirect autoregulation of host genes through modulation of functionally connected gene clusters by intragenic miRNAs was demonstrated. In addition to direct miRNA-to-host gene targeting, intragenic miRNAs also appeared to interact with functionally related genes, thus affecting their host gene function through an indirect autoregulatory mechanism. This strongly argues for the biological relevance of autoregulation not only for the host genes themselves but, more importantly, for the entire gene cluster interacting with the host gene.

scholarly journals Transcription of intragenic CpG islands influences spatiotemporal host gene pre-mRNA processing

2020 ◽  
Author(s):  
Samuele M Amante ◽  
Bertille Montibus ◽  
Michael Cowley ◽  
Nikolaos Barkas ◽  
Jessica Setiadi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Expression Patterns ◽  
Cpg Islands ◽  
Alternative Polyadenylation ◽  
Mrna Processing ◽  
Host Gene ◽  
Independent Manner ◽  
Mammalian Genomes ◽  
Development And Differentiation ◽  
Host Genes

ABSTRACTAlternative splicing (AS) and alternative polyadenylation (APA) generate diverse transcripts in mammalian genomes during development and differentiation. Epigenetic factors such as trimethylation of histone H3 lysine 36 (H3K36me3) and DNA methylation play a role in generating transcriptome diversity. Intragenic CpG islands (iCGIs) and their corresponding host genes exhibit dynamic epigenetic and gene expression patterns during development and between different tissues. We hypothesise that iCGI-associated H3K36me3, DNA methylation and transcription can influence host gene AS and/or APA. We investigate H3K36me3 and find that this histone mark is not a major regulator of AS or APA in our model system. Genomewide, we identify over 4000 host genes that harbour an iCGI in the mammalian genome, including both previously annotated and novel iCGI/host gene pairs. The transcriptional activity of these iCGIs is tissue- and developmental stage-specific and, for the first time, we demonstrate that the premature termination of host gene transcripts upstream of iCGIs is closely correlated with the level of iCGI transcription in a DNA-methylation independent manner. These studies suggest that iCGI transcription, rather than H3K36me3 or DNA methylation, interfere with host gene transcription and pre-mRNA processing genomewide and contributes to the spatiotemporal diversification of both the transcriptome and proteome.

scholarly journals Transcription of intragenic CpG islands influences spatiotemporal host gene pre-mRNA processing

2020 ◽  
Vol 48 (15) ◽  
pp. 8349-8359
Author(s):  
Samuele M Amante ◽  
Bertille Montibus ◽  
Michael Cowley ◽  
Nikolaos Barkas ◽  
Jessica Setiadi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Expression Patterns ◽  
Cpg Islands ◽  
Alternative Polyadenylation ◽  
Mrna Processing ◽  
Host Gene ◽  
Independent Manner ◽  
Mammalian Genomes ◽  
Development And Differentiation ◽  
Host Genes

Abstract Alternative splicing (AS) and alternative polyadenylation (APA) generate diverse transcripts in mammalian genomes during development and differentiation. Epigenetic marks such as trimethylation of histone H3 lysine 36 (H3K36me3) and DNA methylation play a role in generating transcriptome diversity. Intragenic CpG islands (iCGIs) and their corresponding host genes exhibit dynamic epigenetic and gene expression patterns during development and between different tissues. We hypothesise that iCGI-associated H3K36me3, DNA methylation and transcription can influence host gene AS and/or APA. We investigate H3K36me3 and find that this histone mark is not a major regulator of AS or APA in our model system. Genomewide, we identify over 4000 host genes that harbour an iCGI in the mammalian genome, including both previously annotated and novel iCGI/host gene pairs. The transcriptional activity of these iCGIs is tissue- and developmental stage-specific and, for the first time, we demonstrate that the premature termination of host gene transcripts upstream of iCGIs is closely correlated with the level of iCGI transcription in a DNA-methylation independent manner. These studies suggest that iCGI transcription, rather than H3K36me3 or DNA methylation, interfere with host gene transcription and pre-mRNA processing genomewide and contributes to the spatiotemporal diversification of both the transcriptome and proteome.

The Functional Examination of Conserved and Non-conserved lncRNA in Allotetraploid Gossypium hirsutum

2020 ◽  
Author(s):  
Xueying Guan ◽  
Luyao Wang ◽  
Jin Han ◽  
Kening Lu ◽  
Menglin Li ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Evolutionary Model ◽  
Functional Screening ◽  
Virus Induced Gene Silencing ◽  
Protein Coding ◽  
Polyploid Evolution ◽  
Protein Coding Genes ◽  
Cotton Species ◽  
Conservation Level ◽  
Allotetraploid Cotton

Abstract Background The relationship between the lncRNA conservation level and its function is controversial. One of the technique barrier to address this question is how to define the conserved non-coding genes across species.Results We developed an evolutionary model using diploid and allotetraploid cotton species to identify 80% of the non-coding transcripts unique to the allotetraploid cotton in comparison with its diploid ancestors. This led us to define conserved lncRNA and non-conserved lncRNA based on their conservation throughout polyploid evolution. LncRNA expression was preferentially associated with the flanking protein-coding genes, indicating a regulatory role in cis in response to environmental stimuli. However, the conserved and non-conserved lncRNAs showed no difference in their levels of association with the expression of the flanking protein-coding genes. The 111 selected highly expressed conserved and non-conserved lncRNA candidates were subjected to a virus-induced gene silencing operation that was integrated with abiotic stress treatments. From the low-throughput, functional screening pilot test, we obtained candidate lncRNAs related to plant height, tolerance to drought and other abiotic stresses. Conclusions The conservation level of the lncRNAs may impact on their expression patterns and functions as individual case rather than in genome wide.

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