scholarly journals Natural copy number differences of tandemly repeated small nucleolar RNAs in the Prader-Willi syndrome genomic region regulate individual behavioral responses in mammals

2018 ◽  
Author(s):  
Maryam Keshavarz ◽  
Rebecca Krebs-Wheaton ◽  
Peter Refki ◽  
Yoland Savriama ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Gaba Receptors ◽  
Copy Number ◽  
Serotonin Receptor ◽  
Target Genes ◽  
Phenotypic Variability ◽  
Inbred Mouse Strain ◽  
Prader Willi Syndrome ◽  
Small Nucleolar Rnas ◽  
Copy Numbers ◽  
Nucleolar Rnas

AbstractThe Prader-Willi Syndrome (PWS) gene region is an imprinted gene complex involved in behavioral, metabolic and osteogenic functions. We have analyzed here the variation of two families of regulatory small nucleolar RNAs (SNORD115 and SNORD116) that are coded within the PWS and are expressed from the paternal chromosome. They are organized in two tandemly repeated clusters which are naturally copy number variable between individuals. We find that the copy numbers at these loci correlate with repeatable individual test scores for anxiety that are considered to constitute a component of the “personality” of individuals. We show this for different populations and species of mice, cavies and for the anxiety component of personality tests in humans. This is also the case for an inbred mouse strain (C57Bl6) implying that copy number variation creates phenotypic variability even in an isogenic background. In transcriptome data from brain samples of this strain we find SNORD copy-number correlated regulation of target genes that are known to be involved in influencing behavior. SNORD115 has previously been suggested to regulate splicing of the serotonin receptor Htr2c and we confirm this in our data. For SNORD116 we provide evidence that it regulates the expression level of the chromatin regulator Ankrd11, which itself regulates GABA receptors, metabolic pathways, cell differentiation and osteogenesis. Intriguingly, we find that craniofacial shapes in mice correlate also with SNORD116 copy numbers. New copy number variants are generated at very high rates in mice, possibly at every generation, explaining why conventional genetic mapping could not detect this association. Our results suggest that the variable dosage of two regulatory RNAs are major determinants of individual behavioral differences and correlated traits in mammals.

scholarly journals When small RNAs become smaller: non - canonical functions of snoRNAs and their derivatives

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Anna Maria Mleczko ◽  
Kamilla Bąkowska-Żywicka
Keyword(s):  
Alternative Splicing ◽  
Small Rnas ◽  
Metabolic Stress ◽  
Full Length ◽  
Human Diseases ◽  
Cajal Bodies ◽  
Prader Willi Syndrome ◽  
Small Nucleolar Rnas ◽  
Stress Regulation ◽  
Nucleolar Rnas

Small nucleolar RNAs (snoRNAs) are molecules placed in the cell nucleolus and in Cajal bodies. Many scientific reports clearly show that snoRNAs are not only responsible for modifications of other RNAs but also possess multiple other functions such as metabolic stress regulation or modulation of alternative splicing. Full-length snoRNAs as well as small RNAs derived from snoRNAs have been implied in human diseases such as cancer or Prader – Willi Syndrome.  In this review we would like to describe these non – canonical roles of snoRNAs and their derivatives  with the emphasis on their role in human diseases. 

scholarly journals Evidence for the Role of PWCR1/HBII-85 C/D Box Small Nucleolar RNAs in Prader-Willi Syndrome

2002 ◽  
Vol 71 (3) ◽  
pp. 669-678 ◽  
Author(s):  
Renata C. Gallagher ◽  
Birgit Pils ◽  
Mohammed Albalwi ◽  
Uta Francke
Keyword(s):  
Prader Willi Syndrome ◽  
Small Nucleolar Rnas ◽  
Nucleolar Rnas

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 Development and interlaboratory evaluation of a NIST Reference Material RM 8366 for EGFR and MET gene copy number measurements

2019 ◽  
Vol 57 (8) ◽  
pp. 1142-1152 ◽  
Author(s):  
Hua-Jun He ◽  
Biswajit Das ◽  
Megan H. Cleveland ◽  
Li Chen ◽  
Corinne E. Camalier ◽  
...  
Keyword(s):  
Reference Material ◽  
Copy Number ◽  
Target Genes ◽  
Human Cancer ◽  
Gene Copy Number ◽  
Digital Pcr ◽  
Cancer Diagnostics ◽  
Gene Copy ◽  
Human Cancer Cell Lines ◽  
Copy Numbers

Abstract Background The National Institute of Standards and Technology (NIST) Reference Material RM 8366 was developed to improve the quality of gene copy measurements of EGFR (epidermal growth factor receptor) and MET (proto-oncogene, receptor tyrosine kinase), important targets for cancer diagnostics and treatment. The reference material is composed of genomic DNA prepared from six human cancer cell lines with different levels of amplification of the target genes. Methods The reference values for the ratios of the EGFR and MET gene copy numbers to the copy numbers of reference genes were measured using digital PCR. The digital PCR measurements were confirmed by two additional laboratories. The samples were also characterized using Next Generation Sequencing (NGS) methods including whole genome sequencing (WGS) at three levels of coverage (approximately 1 ×, 5 ×  and greater than 30 ×), whole exome sequencing (WES), and two different pan-cancer gene panels. The WES data were analyzed using three different bioinformatic algorithms. Results The certified values (digital PCR) for EGFR and MET were in good agreement (within 20%) with the values obtained from the different NGS methods and algorithms for five of the six components; one component had lower NGS values. Conclusions This study shows that NIST RM 8366 is a valuable reference material to evaluate the performance of assays that assess EGFR and MET gene copy number measurements.

scholarly journals ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs

2005 ◽  
Vol 169 (5) ◽  
pp. 745-753 ◽  
Author(s):  
Patrice Vitali ◽  
Eugenia Basyuk ◽  
Elodie Le Meur ◽  
Edouard Bertrand ◽  
Françoise Muscatelli ◽  
...  
Keyword(s):  
Rna Editing ◽  
Serotonin Receptor ◽  
Small Nucleolar Rnas ◽  
Ribonucleoprotein Particle ◽  
Subcellular Targeting ◽  
Adenosine Deaminases ◽  
Bona Fide ◽  
Cellular Compartments ◽  
Nucleolar Rna ◽  
Nucleolar Rnas

Posttranscriptional, site-specific adenosine to inosine (A-to-I) base conversions, designated as RNA editing, play significant roles in generating diversity of gene expression. However, little is known about how and in which cellular compartments RNA editing is controlled. Interestingly, the two enzymes that catalyze RNA editing, adenosine deaminases that act on RNA (ADAR) 1 and 2, have recently been demonstrated to dynamically associate with the nucleolus. Moreover, we have identified a brain-specific small RNA, termed MBII-52, which was predicted to function as a nucleolar C/D RNA, thereby targeting an A-to-I editing site (C-site) within the 5-HT2C serotonin receptor pre-mRNA for 2′-O-methylation. Through the subcellular targeting of minigenes that contain natural editing sites, we show that ADAR2- but not ADAR1-mediated RNA editing occurs in the nucleolus. We also demonstrate that MBII-52 forms a bona fide small nucleolar ribonucleoprotein particle that specifically decreases the efficiency of RNA editing by ADAR2 at the targeted C-site. Our data are consistent with a model in which C/D small nucleolar RNA might play a role in the regulation of RNA editing.

scholarly journals 01-P010 Prader–Willi Syndrome and small nucleolar RNAs

2009 ◽  
Vol 126 ◽  
pp. S53-S54
Author(s):  
Carolin Purmann ◽  
Giles Yeo ◽  
Sadaf Farooqi ◽  
Stephen O’Rahilly
Keyword(s):  
Prader Willi Syndrome ◽  
Small Nucleolar Rnas ◽  
Nucleolar Rnas

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 Accucopy: accurate and fast inference of allele-specific copy number alterations from low-coverage low-purity tumor sequencing data

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xinping Fan ◽  
Guanghao Luo ◽  
Yu S. Huang
Keyword(s):  
Copy Number ◽  
Bayesian Learning ◽  
Kernel Smoothing ◽  
Gaussian Mixture ◽  
Copy Number Alterations ◽  
Sequencing Data ◽  
Copy Numbers ◽  
Allele Specific ◽  
Tumor Sequencing ◽  
Low Coverage

Abstract Background Copy number alterations (CNAs), due to their large impact on the genome, have been an important contributing factor to oncogenesis and metastasis. Detecting genomic alterations from the shallow-sequencing data of a low-purity tumor sample remains a challenging task. Results We introduce Accucopy, a method to infer total copy numbers (TCNs) and allele-specific copy numbers (ASCNs) from challenging low-purity and low-coverage tumor samples. Accucopy adopts many robust statistical techniques such as kernel smoothing of coverage differentiation information to discern signals from noise and combines ideas from time-series analysis and the signal-processing field to derive a range of estimates for the period in a histogram of coverage differentiation information. Statistical learning models such as the tiered Gaussian mixture model, the expectation–maximization algorithm, and sparse Bayesian learning were customized and built into the model. Accucopy is implemented in C++ /Rust, packaged in a docker image, and supports non-human samples, more at http://www.yfish.org/software/. Conclusions We describe Accucopy, a method that can predict both TCNs and ASCNs from low-coverage low-purity tumor sequencing data. Through comparative analyses in both simulated and real-sequencing samples, we demonstrate that Accucopy is more accurate than Sclust, ABSOLUTE, and Sequenza.

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