Small nucleolar RNAS in OA pathogenesis and cartilage biology

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.

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Site-Specific Pseudouridine Formation in Preribosomal RNA Is Guided by Small Nucleolar RNAs

Cell ◽

10.1016/s0092-8674(00)80263-9 ◽

1997 ◽

Vol 89 (5) ◽

pp. 799-809 ◽

Cited By ~ 342

Author(s):

Philippe Ganot ◽

Marie-Line Bortolin ◽

Tamás Kiss

Keyword(s):

Small Nucleolar Rnas ◽

Site Specific ◽

Nucleolar Rnas

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Three new small nucleolar RNAs that are psoralen cross-linked in vivo to unique regions of pre-rRNA

Molecular and Cellular Biology ◽

10.1128/mcb.13.7.4382-4390.1993 ◽

1993 ◽

Vol 13 (7) ◽

pp. 4382-4390

Author(s):

O J Rimoldi ◽

B Raghu ◽

M K Nag ◽

G L Eliceiri

Keyword(s):

Small Rnas ◽

18S Rrna ◽

Rnase H ◽

Antisense Oligodeoxynucleotide ◽

28S Rrna ◽

Small Nucleolar Rnas ◽

Rrna Sequence ◽

Nucleolar Rna ◽

Nucleolar Rnas

We have recently described three novel human small nucleolar RNA species with unique nucleotide sequences, which were named E1, E2, and E3. The present article describes specific psoralen photocross-linking in whole HeLa cells of E1, E2, and E3 RNAs to nucleolar pre-rRNA. These small RNAs were cross-linked to different sections of pre-rRNA. E1 RNA was cross-linked to two segments of nucleolar pre-rRNA; one was within residues 697 to 1163 of the 5' external transcribed spacer, and the other one was between nucleotides 664 and 1021 of the 18S rRNA sequence. E2 RNA was cross-linked to a region within residues 3282 to 3667 of the 28S rRNA sequence. E3 RNA was cross-linked to a sequence between positions 1021 and 1639 of the 18S rRNA sequence. Primer extension analysis located psoralen adducts in E1, E2, and E3 RNAs that were enriched in high-molecular-weight fractions of nucleolar RNA. Some of these psoralen adducts might be cross-links of E1, E2, and E3 RNAs to large nucleolar RNA. Antisense oligodeoxynucleotide-targeted RNase H digestion of nucleolar extracts revealed accessible segments in these three small RNAs. The accessible regions were within nucleotide positions 106 to 130 of E1 RNA, positions 24 to 48 and 42 to 66 of E2 RNA, and positions 7 to 16 and about 116 to 122 of E3 RNA. Some of the molecules of these small nucleolar RNAs sedimented as if associated with larger structures when both nondenatured RNA and a nucleolar extract were analyzed.

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Abstract 15984: Rpl13a Small Nucleolar RNAs Promote Oxidative Stress and Atherosclerosis

Circulation ◽

10.1161/circ.142.suppl_3.15984 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Lisheng Zhang ◽

Jiaohui Wu ◽

Andrew J Vista ◽

Leigh Brian ◽

Yushi Bai ◽

...

Keyword(s):

Oxidative Stress ◽

Carotid Arteries ◽

Neointimal Hyperplasia ◽

Foam Cells ◽

Slice Thickness ◽

Small Nucleolar Rnas ◽

And Migration ◽

Nucleolar Rnas ◽

Proliferation And Migration

Reactive oxygen species (ROS) contribute to atherogenesis. An unusual mechanism that increases cellular ROS levels and oxidative stress involves 4 ubiquitously expressed noncoding small nucleolar RNAs (snoRNAs) from introns of the ribosomal protein L13a ( Rpl13a ) locus: U32a , U33 , U34 , and U35a . We tested the hypothesis that these snoRNAs promote aortic smooth muscle cell (SMC) activation and vascular inflammation, by using “snoKO” mice with targeted deletion of the 4 snoRNAs (but not Rpl13a ). Compared with congenic WT SMCs, snoKO SMCs showed 40±20% lower ROS levels, assessed by DCF fluorescence ( p <0.02). Congruently, ROS levels were 35±5% lower in snoKO than WT aorta and carotid frozen sections ( p <0.01), assessed by CellROX Orange fluorescence. Proliferation and migration evoked by FBS and PDGF-BB, respectively, were each 30±10% less in snoKO than WT SMCs ( p <0.01 for each). To assess SMC migration and proliferation in vivo, we performed carotid artery endothelial denudation. Before injury, snoKO and WT carotid arteries were morphologically equivalent. Four wk after injury, carotid neointimal hyperplasia was 57±9% less and luminal area was 40±20 % more in snoKO than in WT mice ( p <0.01). WT and snoKO mice had equivalent heart rates and systolic blood pressures by tail-cuff plethysmography: 480±20 vs 420±80 beats/min; 133±5, 132±7 mm Hg, respectively (n=5/group). To test whether snoRNAs affect atherosclerosis, we orthotopically transplanted carotid arteries from WT and snoKO mice into congenic Apoe -/- mice. Six wk post-op, atherosclerotic neointima was 70±10% smaller in snoKO than in WT carotids ( p <0.01). To assess SMC-to-foam-cell transdifferentiation, which is ROS-dependent, carotid cross-sections were stained for apoE to identify graft-derived cells and for cholesteryl ester with BODIPY. BODIPY + foam cells comprised 21±3% and 11±7% of neointimal area in WT and snoKO carotids, respectively ( p <0.05). Confocal co-localization of apoE and BODIPY (optical slice thickness 1 μm) showed that graft-derived foam cells were 2.0±0.6-fold more prevalent in WT than in snoKO carotids ( p <0.01). We conclude that Rpl13a snoRNAs promote SMC ROS levels, proliferation and migration in vitro and in vivo, and that these snoRNAs augment atherosclerosis.

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Knock-Down of a Novel snoRNA in Tetrahymena Reveals a Dual Role in 5.8S rRNA Processing and Generation of a 26S rRNA Fragment

Biomolecules ◽

10.3390/biom8040128 ◽

2018 ◽

Vol 8 (4) ◽

pp. 128

Author(s):

Kasper Andersen ◽

Henrik Nielsen

Keyword(s):

Small Nucleolar Rnas ◽

Rrna Processing ◽

Specific Chemical ◽

Knock Down ◽

5.8S Rrna ◽

Rrna Species ◽

26S Rrna ◽

Precursor Molecules ◽

Nucleolar Rnas ◽

Function Sequence

In eukaryotes, 18S, 5.8S, and 28S rRNAs are transcribed as precursor molecules that undergo extensive modification and nucleolytic processing to form the mature rRNA species. Central in the process are the small nucleolar RNAs (snoRNAs). The majority of snoRNAs guide site specific chemical modifications but a few are involved in defining pre-rRNA cleavages. Here, we describe an unusual snoRNA (TtnuCD32) belonging to the box C/D subgroup from the ciliate Tetrahymena thermophila. We show that TtnuCD32 is unlikely to function as a modification guide snoRNA and that it is critical for cell viability. Cell lines with genetic knock-down of TtnuCD32 were impaired in growth and displayed two novel and apparently unrelated phenotypes. The most prominent phenotype is the accumulation of processing intermediates of 5.8S rRNA. The second phenotype is the decrease in abundance of a ~100 nt 26S rRNA fragment of unknown function. Sequence analysis demonstrated that TtnuCD32 share features with the essential snoRNA U14 but an alternative candidate (TtnuCD25) was more closely related to other U14 sequences. This, together with the fact that the observed rRNA processing phenotypes were not similar to what has been observed in U14 depleted cells, suggests that TtnuCD32 is a U14 homolog that has gained novel functions.

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Genome-Wide Identification and Analysis of Small Nucleolar RNAs and Their Roles in Regulating Latex Regeneration in the Rubber Tree (Hevea brasiliensis)

Frontiers in Plant Science ◽

10.3389/fpls.2021.731484 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiang Chen ◽

Zhi Deng ◽

Dingwei Yu ◽

Xiaofei Zhang ◽

Zewei An ◽

...

Keyword(s):

Rubber Tree ◽

Computational Prediction ◽

Total Solid ◽

Solid Content ◽

Small Nucleolar Rnas ◽

Rna Seq ◽

Total Solid Content ◽

Nuclear Rna ◽

Latex Regeneration ◽

Nucleolar Rnas

Small nucleolar RNAs (snoRNAs) are a class of conserved nuclear RNAs that play important roles in the modification of ribosomal RNAs (rRNAs) in plants. In rubber trees, rRNAs are run off with latex flow during tapping and need to be regenerated for maintaining the functions of the laticifer cells. SnoRNAs are expected to play essential roles in the regeneration of rRNAs. However, snoRNAs in the rubber tree have not been sufficiently characterized thus far. In this study, we performed nuclear RNA sequencing (RNA-seq) to identify snoRNAs globally and investigate their roles in latex regeneration. We identified a total of 3,626 snoRNAs by computational prediction with nuclear RNA-seq data. Among these snoRNAs, 50 were highly expressed in latex; furthermore, the results of reverse transcription polymerase chain reaction (RT-PCR) showed the abundant expression of 31 of these snoRNAs in latex. The correlation between snoRNA expression and adjusted total solid content (TSC/C) identified 13 positively yield-correlated snoRNAs. To improve the understanding of latex regeneration in rubber trees, we developed a novel insulated tapping system (ITS), which only measures the latex regenerated in specific laticifers. Using this system, a laticifer-abundant snoRNA, HbsnoR28, was found to be highly correlated with latex regeneration. To the best of our knowledge, this is the first report to globally identify snoRNAs that might be involved in latex regeneration regulation and provide new clues for unraveling the mechanisms underlying the regulation of latex regeneration.

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Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia

BMC Medical Genomics ◽

10.1186/1755-8794-6-27 ◽

2013 ◽

Vol 6 (1) ◽

Cited By ~ 39

Author(s):

Domenica Ronchetti ◽

Laura Mosca ◽

Giovanna Cutrona ◽

Giacomo Tuana ◽

Massimo Gentile ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

Small Nucleolar Rnas ◽

New Biomarkers ◽

Nucleolar Rnas

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

International Journal of Molecular Sciences ◽

10.3390/ijms21072611 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2611 ◽

Cited By ~ 1

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.

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