Neutral evolution of snoRNA Host Gene long non-coding RNA affects cell fate control
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ABSTRACT:
PROVIDER: PRJNA1099903 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28673916_1.fastq.gz | Fastqsanger.gz | |||
| SRR28673916_2.fastq.gz | Fastqsanger.gz | |||
| SRR28673917_1.fastq.gz | Fastqsanger.gz | |||
| SRR28673917_2.fastq.gz | Fastqsanger.gz | |||
| SRR28673918_1.fastq.gz | Fastqsanger.gz |
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Project description:A fundamental challenge in molecular biology is to understand how evolving genomes can acquire new functions. Several recent studies have underscored how non-conserved sequences can contribute to organismal diversification in the primate lineage. Actively transcribed, non-coding parts of the genome provide a potential platform for the development of new functional sequences, but their biological and evolutionary roles remain largely unexplored. Here we show that a set of neutrally evolving long non-coding RNAs (lncRNA) arising from small nucleolar RNA Host Genes (SNHGs) are highly expressed in skin and dysregulated in inflammatory conditions. Using SNHG7 and human epidermal keratinocytes as a model, we describe a mechanism by which these lncRNAs can increase self-renewal and inhibit differentiation. SNHG7 lncRNA’s activity has been acquired recently in the primate lineage and depends on a short sequence required for microRNA binding. Taken together, our results highlight the importance of understanding the role of fast-evolving transcripts in normal and diseased epithelia, and show how poorly conserved, actively transcribed non-coding sequences can participate in the evolution of genomic functionality.
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Project description:ncRNA expression, including snoRNAs, across 11 tissues using polyA-neutral amplification Non-coding RNAs (ncRNAs) are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6) is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I) cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available. ArrayExpress Release Date: 2010-07-05 Publication Title: ncRNA expression, including snoRNAs, across 11 tissues using polyA-neutral amplification Publication Author List: Matthew Biery,Heather Bouzek,Ronghua Chen,Stuart Jackson,Jason M. Johnson,Carol A. Rohl,Chris K. Raymond,David Haynor,Christopher D. Armour,John C. Castle Person Roles: submitter Person Last Name: Loewer Person First Name: Martin Person Mid Initials: Person Email: martin.loewer@tron-mainz.de Person Phone: +49 6131-720298-11 Person Address: TRON Translationale Onkologie gGmbH, Langenbeckstr. 8, D-55131 Mainz Person Affiliation: TRON
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2015-04-04 | E-GEOD-67569 | biostudies-arrayexpress
Project description:Small nucleolar RNAs (snoRNA) are non-coding RNAs known for guiding RNA modifications including 2ʹ-O-methylation (Nm) and pseudouridine (Ψ). While snoRNAs may also interact with other RNAs such as mRNA, the full repertoire of RNAs targeted by snoRNA remains elusive due to the lack of effective technologies that identify snoRNA targets transcriptome-wide. Here we develop a chemical crosslinking-based approach that comprehensively detects cellular RNA targets of snoRNAs, yielding thousands of previously unrecognized snoRNA-mRNA interactions in human cells and mouse brain tissues. Many interactions occur outside of snoRNA-guided rRNA modification sites, hinting at non-canonical functions beyond RNA modification. We find that one of these snoRNAs, SNORA73, targets mRNAs that encode secretory proteins and membrane proteins. SNORA73 also interacts with 7SL RNA, part of the signal recognition particle (SRP) required for protein secretion. The mRNA-SNORA73-7SL RNA interactions enhance the association of the SNORA73-target mRNAs with SRP, thereby facilitating secretion of the encoded proteins.
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Project description:Trypanosomes are unicellular parasites that cycle between the insect and mammalian host and is the causative agent of African sleeping sickness and the wasting disease, nagana, in cattle. Previous studies from our lab suggested that individual rRNA modification such as pseudouridine (Y) and 2’-O-methylation are developmentally regulated during the complex life cycle of these parasites. In this study we identified that the Y composition of translating ribosomes are different from rRNA derived from total RNA. Ablation of single snoRNA guiding Y in one of the inter-subunit bridges of the ribosome affects its affinity to translate specific mRNA. Mutational analysis in the pseudouridylation pocket of this snoRNA supports for the notion that the guided modification and not the chaperonic activity, is essential for the observed phenotype. Structural probing of rRNA using DMS-seq suggested that a single modification can affect the rRNA structure locally as wells as globally. Quantitative profiling of the composition of mutant ribosomes suggested the absence of eS12 ribosomal protein in the mature ribosomes. Addback experiments validated the role of eS12 during the loss of a single Y in these mutant cells. Orthologous experiments in related leishmania spp. also verify importance of a single Y in the function of ribosome. Ongoing experiments intend to visualize such ribosomes lacking a single RNA modification and decipher their significance towards ribosome structure.
2024-01-26 | PXD030544 | Pride
Project description: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. 59% 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.
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