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

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. 

1993 ◽  
Vol 13 (7) ◽  
pp. 4382-4390
Author(s):  
O J Rimoldi ◽  
B Raghu ◽  
M K Nag ◽  
G L Eliceiri

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.


2011 ◽  
Vol 14 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Carlos I. Michel ◽  
Christopher L. Holley ◽  
Benjamin S. Scruggs ◽  
Rohini Sidhu ◽  
Rita T. Brookheart ◽  
...  

2002 ◽  
Vol 71 (3) ◽  
pp. 669-678 ◽  
Author(s):  
Renata C. Gallagher ◽  
Birgit Pils ◽  
Mohammed Albalwi ◽  
Uta Francke

2001 ◽  
Vol 152 (6) ◽  
pp. 1279-1288 ◽  
Author(s):  
Yi-Tao Yu ◽  
Mei-Di Shu ◽  
Aarthi Narayanan ◽  
Rebecca M. Terns ◽  
Michael P. Terns ◽  
...  

U2 small nuclear (sn)RNA contains a large number of posttranscriptionally modified nucleotides, including a 5′ trimethylated guanosine cap, 13 pseudouridines, and 10 2′-O-methylated residues. Using Xenopus oocytes, we demonstrated previously that at least some of these modified nucleotides are essential for biogenesis of a functional snRNP. Here we address the subcellular site of U2 internal modification. Upon injection into the cytoplasm of oocytes, G-capped U2 that is transported to the nucleus becomes modified, whereas A-capped U2 that remains in the cytoplasm is not modified. Furthermore, by injecting U2 RNA into isolated nuclei or enucleated oocytes, we observe that U2 internal modifications occur exclusively in the nucleus. Analysis of the intranuclear localization of fluorescently labeled RNAs shows that injected wild-type U2 becomes localized to nucleoli and Cajal bodies. Both internal modification and nucleolar localization of U2 are dependent on the Sm binding site. An Sm-mutant U2 is targeted only to Cajal bodies. The Sm binding site can be replaced by a nucleolar localization signal derived from small nucleolar RNAs (the box C/D motif), resulting in rescue of internal modification as well as nucleolar localization. Analysis of additional chimeric U2 RNAs reveals a correlation between internal modification and nucleolar localization. Together, our results suggest that U2 internal modification occurs within the nucleolus.


2010 ◽  
Vol 38 (2) ◽  
pp. 672-676 ◽  
Author(s):  
Julie Rodor ◽  
Ingrid Letelier ◽  
Loreto Holuigue ◽  
Manuel Echeverria

The snoRNAs (small nucleolar RNAs) and related scaRNAs (small RNAs in the Cajal bodies) represent a major class of nuclear RNAs that guide 2′-O-ribose methylation and pseudouridylation of rRNAs, snRNAs (small nuclear RNAs) and other RNA targets. In vivo, all snoRNAs associate with a set of four highly conserved nucleolar proteins, forming the functional snoRNPs (small nucleolar ribonucleoproteins). The core structure of these mature snoRNPs has now been well described in eukaryotes, but less is known of their biogenesis. Recent data in animals and yeast reveal that assembly of the snoRNPs is a complex process that implicates several auxiliary proteins and transient protein–protein interactions. This new level of snoRNP regulation is now beginning to be unravelled in animals and yeast, but remains unexplored in plants. In the present paper, we review recent data from genomic and functional analysis allowing the identification and study of factors controlling the biogenesis of plant snoRNPs and their impact on plant development.


2021 ◽  
Vol 8 ◽  
Author(s):  
Kotaro Nakanishi

The biosynthesis pathways of microRNAs (miRNAs) have been well characterized with the identification of the required components. miRNAs are synthesized from the transcripts of miRNA genes and other RNAs, such as introns, transfer RNAs, ribosomal RNAs, small nucleolar RNAs, and even viral miRNAs. These small RNAs are loaded into Argonaute (AGO) proteins and recruit the effector complexes to target mRNAs, repressing their gene expression post-transcriptionally. While mature miRNAs were defined as 19–23 nucleotides (nt), tiny RNAs (tyRNAs) shorter than 19 nt have been found to bind AGOs as equivalent or lesser miRNAs compared to their full-length mature miRNAs. In contrast, my recent study revealed that when human AGO3 loads 14 nt cleavage-inducing tyRNAs (cityRNAs), comprised of the first 14 nt of their corresponding mature miRNA, it can become a comparable slicer to AGO2. This observation raises the possibility that tyRNAs play distinct roles from their mature form. This minireview focuses on human AGO-associated tyRNAs shorter than 19 nt and discusses their possible biosynthesis pathways and physiological benefits, including how tyRNAs could avoid target-directed miRNA degradation accompanied by AGO polyubiquitination.


2009 ◽  
Vol 126 ◽  
pp. S53-S54
Author(s):  
Carolin Purmann ◽  
Giles Yeo ◽  
Sadaf Farooqi ◽  
Stephen O’Rahilly

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Jane E. Freedman ◽  
Mark Gerstein ◽  
Eric Mick ◽  
Joel Rozowsky ◽  
Daniel Levy ◽  
...  

Abstract There is growing appreciation for the importance of non-protein-coding genes in development and disease. Although much is known about microRNAs, limitations in bioinformatic analyses of RNA sequencing have precluded broad assessment of other forms of small-RNAs in humans. By analysing sequencing data from plasma-derived RNA from 40 individuals, here we identified over a thousand human extracellular RNAs including microRNAs, piwi-interacting RNA (piRNA), and small nucleolar RNAs. Using a targeted quantitative PCR with reverse transcription approach in an additional 2,763 individuals, we characterized almost 500 of the most abundant extracellular transcripts including microRNAs, piRNAs and small nucleolar RNAs. The presence in plasma of many non-microRNA small-RNAs was confirmed in an independent cohort. We present comprehensive data to demonstrate the broad and consistent detection of diverse classes of circulating non-cellular small-RNAs from a large population.


2018 ◽  
Author(s):  
Maryam Keshavarz ◽  
Rebecca Krebs-Wheaton ◽  
Peter Refki ◽  
Yoland Savriama ◽  
Yi Zhang ◽  
...  

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.


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