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 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 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 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 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 The Host Gene for Intronic U17 Small Nucleolar RNAs in Mammals Has No Protein-Coding Potential and Is a Member of the 5′-Terminal Oligopyrimidine Gene Family

1998 ◽  
Vol 18 (8) ◽  
pp. 4509-4518 ◽  
Author(s):  
Pawel Pelczar ◽  
Witold Filipowicz
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Transcription Unit ◽  
Host Gene ◽  
Small Nucleolar Rnas ◽  
Ribosomal Protein Genes ◽  
Protein Coding ◽  
Genes Encoding ◽  
Terminal Oligopyrimidine ◽  
Nucleolar Rnas

ABSTRACT Intron-encoded U17a and U17b RNAs are members of the H/ACA-box class of small nucleolar RNAs (snoRNAs) participating in rRNA processing and modification. We have investigated the organization and expression of the U17 locus in human cells and found that intronic U17a and U17b sequences are transcribed as part of the three-exon transcription unit, named U17HG, positioned approximately 9 kb upstream of the RCC1 locus. Comparison of the human and mouse U17HG genes has revealed that snoRNA-encoding intron sequences but not exon sequences are conserved between the two species and that neither human nor mouse spliced U17HGpoly(A)+ RNAs have the potential to code for proteins. Analyses of polysome profiles and effects of translation inhibitors on the abundance of U17HG RNA in HeLa cells indicated that despite its cytoplasmic localization, little if any U17HGRNA is associated with polysomes. This distinguishes U17HGRNA from another non-protein-coding snoRNA host gene product,UHG RNA, described previously (K. T. Tycowski, M. D. Shu, and J. A. Steitz, Nature 379:464–466, 1996). Determination of the 5′ terminus of the U17HG RNA revealed that transcription of the U17HG gene starts with a C residue followed by a polypyrimidine tract, making this gene a member of the 5′-terminal oligopyrimidine (5′TOP) family, which includes genes encoding ribosomal proteins and some translation factors. Interestingly, other known snoRNA host genes, including theUHG gene (Tycowski et al., op. cit.), have features of the 5′TOP genes. Similar characteristics of the transcription start site regions in snoRNA host and ribosomal protein genes raise the possibility that expression of components of ribosome biogenesis and translational machineries is coregulated.

scholarly journals Emerging Data on the Diversity of Molecular Mechanisms Involving C/D snoRNAs

2021 ◽  
Vol 7 (2) ◽  
pp. 30
Author(s):  
Laeya Baldini ◽  
Bruno Charpentier ◽  
Stéphane Labialle
Keyword(s):  
Ribosomal Rna ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Accurate Description ◽  
Small Nucleolar Rnas ◽  
Age Of Maturity ◽  
Non Coding Rnas ◽  
And Function ◽  
Nucleolar Rnas

Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are involved in mechanisms that go well beyond this function. Here, we present these pieces of evidence in light of the current comprehension of the molecular mechanisms that control C/D snoRNA expression and function. From this inventory emerges that an accurate description of these activities at a molecular level is required to let the snoRNA field enter in a second age of maturity.

scholarly journals Emerging Roles and Potential Applications of Non-Coding RNAs in Glioblastoma

2020 ◽  
Vol 21 (7) ◽  
pp. 2611 ◽  
Author(s):  
Carlos DeOcesano-Pereira ◽  
Raquel A. C. Machado ◽  
Ana Marisa Chudzinski-Tavassi ◽  
Mari Cleide Sogayar
Keyword(s):  
Cancer Type ◽  
Biological Processes ◽  
Small Nucleolar Rnas ◽  
Physiological Conditions ◽  
Master Regulators ◽  
Potential Applications ◽  
Non Coding Rnas ◽  
Regulatory Rnas ◽  
Nucleolar Rnas ◽  
Substantial Effort

Non-coding RNAs (ncRNAs) comprise a diversity of RNA species, which do not have the potential to encode proteins. Non-coding RNAs include two classes of RNAs, namely: short regulatory ncRNAs and long non-coding RNAs (lncRNAs). The short regulatory RNAs, containing up to 200 nucleotides, include small RNAs, such as microRNAs (miRNA), short interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs). The lncRNAs include long antisense RNAs and long intergenic RNAs (lincRNAs). Non-coding RNAs have been implicated as master regulators of several biological processes, their expression being strictly regulated under physiological conditions. In recent years, particularly in the last decade, substantial effort has been made to investigate the function of ncRNAs in several human diseases, including cancer. Glioblastoma is the most common and aggressive type of brain cancer in adults, with deregulated expression of small and long ncRNAs having been implicated in onset, progression, invasiveness, and recurrence of this tumor. The aim of this review is to guide the reader through important aspects of miRNA and lncRNA biology, focusing on the molecular mechanism associated with the progression of this highly malignant cancer type.

scholarly journals LncExpDB: an expression database of human long non-coding RNAs

2020 ◽  
Vol 49 (D1) ◽  
pp. D962-D968 ◽  
Author(s):  
Zhao Li ◽  
Lin Liu ◽  
Shuai Jiang ◽  
Qianpeng Li ◽  
Changrui Feng ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Biological Functions ◽  
Protein Coding ◽  
Web Interfaces ◽  
Functional Studies ◽  
Protein Coding Genes ◽  
Genes Expression ◽  
Wide Range ◽  
Non Coding Rnas ◽  
User Friendly

Abstract Expression profiles of long non-coding RNAs (lncRNAs) across diverse biological conditions provide significant insights into their biological functions, interacting targets as well as transcriptional reliability. However, there lacks a comprehensive resource that systematically characterizes the expression landscape of human lncRNAs by integrating their expression profiles across a wide range of biological conditions. Here, we present LncExpDB (https://bigd.big.ac.cn/lncexpdb), an expression database of human lncRNAs that is devoted to providing comprehensive expression profiles of lncRNA genes, exploring their expression features and capacities, identifying featured genes with potentially important functions, and building interactions with protein-coding genes across various biological contexts/conditions. Based on comprehensive integration and stringent curation, LncExpDB currently houses expression profiles of 101 293 high-quality human lncRNA genes derived from 1977 samples of 337 biological conditions across nine biological contexts. Consequently, LncExpDB estimates lncRNA genes’ expression reliability and capacities, identifies 25 191 featured genes, and further obtains 28 443 865 lncRNA-mRNA interactions. Moreover, user-friendly web interfaces enable interactive visualization of expression profiles across various conditions and easy exploration of featured lncRNAs and their interacting partners in specific contexts. Collectively, LncExpDB features comprehensive integration and curation of lncRNA expression profiles and thus will serve as a fundamental resource for functional studies on human lncRNAs.

scholarly journals Emerging Roles of Estrogen-Regulated Enhancer and Long Non-Coding RNAs

2020 ◽  
Vol 21 (10) ◽  
pp. 3711
Author(s):  
Melina J. Sedano ◽  
Alana L. Harrison ◽  
Mina Zilaie ◽  
Chandrima Das ◽  
Ramesh Choudhari ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Expression Patterns ◽  
Biological Significance ◽  
Rna Seq ◽  
Biological Functions ◽  
Protein Coding ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Non Coding Rnas

Genome-wide RNA sequencing has shown that only a small fraction of the human genome is transcribed into protein-coding mRNAs. While once thought to be “junk” DNA, recent findings indicate that the rest of the genome encodes many types of non-coding RNA molecules with a myriad of functions still being determined. Among the non-coding RNAs, long non-coding RNAs (lncRNA) and enhancer RNAs (eRNA) are found to be most copious. While their exact biological functions and mechanisms of action are currently unknown, technologies such as next-generation RNA sequencing (RNA-seq) and global nuclear run-on sequencing (GRO-seq) have begun deciphering their expression patterns and biological significance. In addition to their identification, it has been shown that the expression of long non-coding RNAs and enhancer RNAs can vary due to spatial, temporal, developmental, or hormonal variations. In this review, we explore newly reported information on estrogen-regulated eRNAs and lncRNAs and their associated biological functions to help outline their markedly prominent roles in estrogen-dependent signaling.

scholarly journals SnoRNA microarray analysis reveals changes in H/ACA and C/D RNA levels caused by dyskerin ablation in mouse liver

2010 ◽  
Vol 429 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Jingping Ge ◽  
Seth D. Crosby ◽  
Michael E. Heinz ◽  
Monica Bessler ◽  
Philip J. Mason
Keyword(s):  
Microarray Analysis ◽  
Mouse Liver ◽  
Cellular Response ◽  
Ribosome Biogenesis ◽  
Microarray Platform ◽  
Protein Component ◽  
Small Nucleolar Rnas ◽  
Ribosome Synthesis ◽  
Nucleolar Rnas ◽  
Host Genes

snoRNAs (small nucleolar RNAs) are key components of snoRNP (small nucleolar ribonucleoprotein) particles involved in modifying specific residues of ribosomal and other RNAs by pseudouridylation (H/ACA snoRNAs) or methylation (C/D snoRNAs). They are encoded within the introns of host genes, which tend to be genes whose products are involved in ribosome biogenesis or function. Although snoRNPs are abundant, ubiquitous and their components highly conserved, information concerning their expression during development or how their expression is altered in diseased states is sparse. To facilitate these studies we have developed a snoRNA microarray platform for the analysis of the abundance of snoRNAs in different RNA samples. In the present study we show that the microarray is sensitive and specific for the detection of snoRNAs. A mouse snoRNA microarray was used to monitor changes in abundance of snoRNAs after ablation of dyskerin, an H/ACA snoRNA protein component, from mouse liver, which causes a decrease in ribosome production. H/ACA snoRNAs were decreased in abundance in these livers while, unexpectedly, C/D snoRNAs were increased. The increase in C/D snoRNAs corresponded with an increase in the abundance of the mRNAs transcribed from snoRNA host genes, suggesting the increase may be part of a cellular response to defective ribosome synthesis.

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