Insights into snoRNA biogenesis and processing from PAR-CLIP of snoRNA core proteins and small RNA sequencing

Kishore, Shivendra; Gruber, Andreas; Jedlinski, Dominik J.; Syed, Afzal Pasha; Jorjani, Hadi; Zavolan, Mihaela

doi:10.1186/gb-2013-14-5-r45

Cited by 122 publications

(187 citation statements)

References 68 publications

(101 reference statements)

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“…S5F). We reanalyzed a massive parallel sequencing data set of small RNAs (Kishore et al 2013) and identified a set of 173 ''active'' snoRNA host genes expressing a total of 242 snoRNAs in HEK293 cells (Supplemental Table S6). For this, we applied an operational definition of a snoRNA host gene as one that produces one or more transcript isoforms with the full snoRNA sequence inside a functional intronic sequence (Kiss et al 2006;Brown et al 2008, Dieci et al 2009).…”

Section: Identification Of Hundreds Of Primary Nmd-responsive Genesmentioning

confidence: 99%

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Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes

et al. 2014

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Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has remained unresolved. Here we used concurrent transcriptome-wide identification of NMD substrates and their 59-39 decay intermediates to establish that SMG6-catalyzed endonucleolysis widely initiates the degradation of human nonsense RNAs, whereas decapping is used to a lesser extent. We also show that a large proportion of genes hosting snoRNAs in their introns produce considerable amounts of NMD-sensitive splice variants, indicating that these RNAs are merely by-products of a primary snoRNA production process. Additionally, transcripts from genes encoding multiple snoRNAs often yield alternative transcript isoforms that allow for differential expression of individual coencoded snoRNAs. Based on our findings, we hypothesize that snoRNA host genes need to be highly transcribed to accommodate high levels of snoRNA production and that the expression of individual snoRNAs and their cognate spliced RNA can be uncoupled via alternative splicing and NMD.[Keywords: RNA decapping; endonucleolytic RNA cleavage; intron-encoded snoRNA; nonsense-mediated decay; regulation of snoRNA expression; snoRNA host genes] Supplemental material is available for this article.Received June 2, 2014; revised version accepted October 3, 2014.All functional transcripts, whether they are proteincoding (mRNA) or noncoding (ncRNA), are produced as precursor molecules that undergo various processing steps before they take on their final forms. Eukaryotic RNA polymerase II transcribed genes often encode more than one mature RNA species, as exemplified by the alternative splicing of exonic sequences into a variety of transcript isoforms (Braunschweig et al. 2013;Kornblihtt et al. 2013), usage of alternative promoters (Carninci et al. 2006), and the hosting of smaller RNAs, like miRNAs and snoRNAs, within introns (Brown et al. 2008). Regulation of such alternative RNA production confers great plasticity to eukaryotic gene expression because parameters such as expression specificity, stability, localization, and protein-coding potential can be altered between transcript isoforms (McGlincy and Smith 2008;Valen et al. 2009;Kelemen et al. 2013). However, many alternative processing options also increase the likelihood of mistakes, and, throughout the life span of a transcript, its integrity and functionality is continuously being monitored, which ensures that nonfunctional processing byproducts and erroneously processed or outworn molecules are degraded by decay machineries residing in either the nucleus or the cytoplasm (Doma and Parker 2007;Muhlemann and Jensen 2012;Arraiano et al. 2013). For cytoplasmic RNAs with mRNA-like characteristics, the distinction between functional and nonfunctional is carried out by means of translation-dependent...

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Section: Identification Of Hundreds Of Primary Nmd-responsive Genesmentioning

confidence: 99%

“…For estimating the expression of snoRNA and miRNA, we used the mapped small RNA data from a previous study (Kishore et al 2013). Expression levels of small RNAs were calculated as the sum of the aligned reads falling within the respective annotations.…”

Section: Small Rna-seq Data Processingmentioning

confidence: 99%

Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes

et al. 2014

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“…6A; Kishore et al 2013) and contains, within its sequence, the predicted human miRNA hsa-mir-3607. e470 represents a previously reported C/D box snoRNA in mouse, designated as SNORD93 (Huttenhofer et al 2001).…”

Section: Differentially Expressed Ncrnas In Young Mice Of the 3xtg Momentioning

confidence: 99%

Generation of a neuro-specific microarray reveals novel differentially expressed noncoding RNAs in mouse models for neurodegenerative diseases

Gstir

Schafferer

Scheideler

et al. 2014

RNA

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We have generated a novel, neuro-specific ncRNA microarray, covering 1472 ncRNA species, to investigate their expression in different mouse models for central nervous system diseases. Thereby, we analyzed ncRNA expression in two mouse models with impaired calcium channel activity, implicated in Epilepsy or Parkinson's disease, respectively, as well as in a mouse model mimicking pathophysiological aspects of Alzheimer's disease. We identified well over a hundred differentially expressed ncRNAs, either from known classes of ncRNAs, such as miRNAs or snoRNAs or which represented entirely novel ncRNA species. Several differentially expressed ncRNAs in the calcium channel mouse models were assigned as miRNAs and target genes involved in calcium signaling, thus suggesting feedback regulation of miRNAs by calcium signaling. In the Alzheimer mouse model, we identified two snoRNAs, whose expression was deregulated prior to amyloid plaque formation. Interestingly, the presence of snoRNAs could be detected in cerebral spine fluid samples in humans, thus potentially serving as early diagnostic markers for Alzheimer's disease. In addition to known ncRNAs species, we also identified 63 differentially expressed, entirely novel ncRNA candidates, located in intronic or intergenic regions of the mouse genome, genomic locations, which previously have been shown to harbor the majority of functional ncRNAs.

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“…Among the snoRNAs, the H/ACA box-type, which forms a typical two-hairpin structure, gives rise to miRNA-like molecules that amount to a few percent of the Argonaute-associated small RNA population [84]. The H/ACA box snoRNA small Cajal body-specific RNA 15 (SCARNA15) generates the most abundant Ago2-associated snoRNA-derived small RNA, which targets the transcript encoding the Mediator coactivator complex subunit cyclin-dependent kinase 19 (CDK19) [29].…”

Section: More Roads Leading To Riscmentioning

confidence: 99%

Seq and CLIP through the miRNA world

Mittal

Zavolan

2014

Genome Biol

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Insights into snoRNA biogenesis and processing from PAR-CLIP of snoRNA core proteins and small RNA sequencing

Cited by 122 publications

References 68 publications

Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes

Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes

Generation of a neuro-specific microarray reveals novel differentially expressed noncoding RNAs in mouse models for neurodegenerative diseases

Seq and CLIP through the miRNA world

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