Small nucleolar RNAs and RNA-guided post-transcriptional modification

2013 ◽  
Vol 54 ◽  
pp. 53-77 ◽  
Author(s):  
Lauren Lui ◽  
Todd Lowe
Keyword(s):  
Rna Processing ◽  
High Throughput Sequencing ◽  
Common Ancestor ◽  
Last Common Ancestor ◽  
Small Nucleolar Rnas ◽  
Ribonucleoprotein Complexes ◽  
Associated Proteins ◽  
Non Coding Rnas ◽  
And Function ◽  
Nucleolar Rnas

snoRNAs (small nucleolar RNAs) constitute one of the largest and best-studied classes of non-coding RNAs that confer enzymatic specificity. With associated proteins, these snoRNAs form ribonucleoprotein complexes that can direct 2′-O-methylation or pseudouridylation of target non-coding RNAs. Aided by computational methods and high-throughput sequencing, new studies have expanded the diversity of known snoRNA functions. Complexes incorporating snoRNAs have dynamic specificity, and include diverse roles in RNA silencing, telomerase maintenance and regulation of alternative splicing. Evidence that dysregulation of snoRNAs can cause human disease, including cancer, indicates that the full scope of snoRNA roles remains an unfinished story. The diversity in structure, genomic origin and function between snoRNAs found in different complexes and among different phyla illustrates the surprising plasticity of snoRNAs in evolution. The ability of snoRNAs to direct highly specific interactions with other RNAs is a consistent thread in their newly discovered functions. Because they are ubiquitous throughout Eukarya and Archaea, it is likely they were a feature of the last common ancestor of these two domains, placing their origin over two billion years ago. In the present chapter, we focus on recent advances in our understanding of these ancient, but functionally dynamic RNA-processing machines.

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 Evolution and function of the hominin forefoot

2018 ◽  
Vol 115 (35) ◽  
pp. 8746-8751 ◽  
Author(s):  
Peter J. Fernández ◽  
Carrie S. Mongle ◽  
Louise Leakey ◽  
Daniel J. Proctor ◽  
Caley M. Orr ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Common Ancestor ◽  
Bipedal Locomotion ◽  
Last Common Ancestor ◽  
Primary Role ◽  
Anthropoid Primates ◽  
And Function ◽  
Metatarsophalangeal Joints ◽  
Selection Of

The primate foot functions as a grasping organ. As such, its bones, soft tissues, and joints evolved to maximize power and stability in a variety of grasping configurations. Humans are the obvious exception to this primate pattern, with feet that evolved to support the unique biomechanical demands of bipedal locomotion. Of key functional importance to bipedalism is the morphology of the joints at the forefoot, known as the metatarsophalangeal joints (MTPJs), but a comprehensive analysis of hominin MTPJ morphology is currently lacking. Here we present the results of a multivariate shape and Bayesian phylogenetic comparative analyses of metatarsals (MTs) from a broad selection of anthropoid primates (including fossil apes and stem catarrhines) and most of the early hominin pedal fossil record, including the oldest hominin for which good pedal remains exist, Ardipithecus ramidus. Results corroborate the importance of specific bony morphologies such as dorsal MT head expansion and “doming” to the evolution of terrestrial bipedalism in hominins. Further, our evolutionary models reveal that the MT1 of Ar. ramidus shifts away from the reconstructed optimum of our last common ancestor with apes, but not necessarily in the direction of modern humans. However, the lateral rays of Ar. ramidus are transformed in a more human-like direction, suggesting that they were the digits first recruited by hominins into the primary role of terrestrial propulsion. This pattern of evolutionary change is seen consistently throughout the evolution of the foot, highlighting the mosaic nature of pedal evolution and the emergence of a derived, modern hallux relatively late in human evolution.

scholarly journals POLIII-derived non-coding RNAs acting as scaffolds and decoys

2019 ◽  
Vol 11 (10) ◽  
pp. 880-885 ◽  
Author(s):  
Hendrik Täuber ◽  
Stefan Hüttelmaier ◽  
Marcel Köhn
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Cellular Functions ◽  
Control Of Gene Expression ◽  
Ribonucleoprotein Complexes ◽  
Small Ncrnas ◽  
Non Coding Rnas ◽  
And Function

Abstract A large variety of eukaryotic small structured POLIII-derived non-coding RNAs (ncRNAs) have been described in the past. However, for only few, e.g. 7SL and H1/MRP families, cellular functions are well understood. For the vast majority of these transcripts, cellular functions remain unknown. Recent findings on the role of Y RNAs and other POLIII-derived ncRNAs suggest an evolutionarily conserved function of these ncRNAs in the assembly and function of ribonucleoprotein complexes (RNPs). These RNPs provide cellular `machineries’, which are essential for guiding the fate and function of a variety of RNAs. In this review, we summarize current knowledge on the role of POLIII-derived ncRNAs in the assembly and function of RNPs. We propose that these ncRNAs serve as scaffolding factors that `chaperone’ RNA-binding proteins (RBPs) to form functional RNPs. In addition or associated with this role, some small ncRNAs act as molecular decoys impairing the RBP-guided control of RNA fate by competing with other RNA substrates. This suggests that POLIII-derived ncRNAs serve essential and conserved roles in the assembly of larger RNPs and thus the control of gene expression by indirectly guiding the fate of mRNAs and lncRNAs.

scholarly journals Fossil hominin shoulders support an African ape-like last common ancestor of humans and chimpanzees

2015 ◽  
Vol 112 (38) ◽  
pp. 11829-11834 ◽  
Author(s):  
Nathan M. Young ◽  
Terence D. Capellini ◽  
Neil T. Roach ◽  
Zeresenay Alemseged
Keyword(s):  
Tool Use ◽  
High Speed ◽  
Common Ancestor ◽  
Modern Human ◽  
Last Common Ancestor ◽  
Ancestral State ◽  
Evolutionary Trajectories ◽  
Parsimonious Model ◽  
And Function ◽  
Fossil Hominin

Reconstructing the behavioral shifts that drove hominin evolution requires knowledge of the timing, magnitude, and direction of anatomical changes over the past ∼6–7 million years. These reconstructions depend on assumptions regarding the morphotype of the Homo–Pan last common ancestor (LCA). However, there is little consensus for the LCA, with proposed models ranging from African ape to orangutan or generalized Miocene ape-like. The ancestral state of the shoulder is of particular interest because it is functionally associated with important behavioral shifts in hominins, such as reduced arboreality, high-speed throwing, and tool use. However, previous morphometric analyses of both living and fossil taxa have yielded contradictory results. Here, we generated a 3D morphospace of ape and human scapular shape to plot evolutionary trajectories, predict ancestral morphologies, and directly test alternative evolutionary hypotheses using the hominin fossil evidence. We show that the most parsimonious model for the evolution of hominin shoulder shape starts with an African ape-like ancestral state. We propose that the shoulder evolved gradually along a single morphocline, achieving modern human-like configuration and function within the genus Homo. These data are consistent with a slow, progressive loss of arboreality and increased tool use throughout human evolution.

scholarly journals Structure and biogenesis of small nucleolar RNAs acting as guides for ribosomal RNA modification.

1999 ◽  
Vol 46 (2) ◽  
pp. 377-389 ◽  
Author(s):  
W Filipowicz ◽  
P Pelczar ◽  
V Pogacic ◽  
F Dragon
Keyword(s):  
Ribosomal Rna ◽  
Structure And Function ◽  
Hydroxyl Group ◽  
Rna Modification ◽  
Small Nucleolar Rnas ◽  
Yeast Saccharomyces Cerevisiae ◽  
Site Specific ◽  
Alternative Pathways ◽  
And Function ◽  
Nucleolar Rnas

Maturation of pre-ribosomal RNA (pre-rRNA) in eukaryotic cells takes place in the nucleolus and involves a large number of cleavage events, which frequently follow alternative pathways. In addition, rRNAs are extensively modified, with the methylation of the 2'-hydroxyl group of sugar residues and conversion of uridines to pseudouridines being the most frequent modifications. Both cleavage and modification reactions of pre-rRNAs are assisted by a variety of small nucleolar RNAs (snoRNAs), which function in the form of ribonucleoprotein particles (snoRNPs). The majority of snoRNAs acts as guides directing site-specific 2'-O-ribose methylation or pseudouridine formation. Over one hundred RNAs of this type have been identified to date in vertebrates and the yeast Saccharomyces cerevisiae. This number is readily explained by the findings that one snoRNA acts as a guide usually for one or at most two modifications, and human rRNAs contain 91 pseudouridines and 106 2'-O-methyl residues. In this article we review information about the biogenesis, structure and function of guide snoRNAs.

scholarly journals jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

2020 ◽  
Author(s):  
Flaria El-Khoury ◽  
Jérôme Bignon ◽  
Jean-René Martin
Keyword(s):  
Cell Proliferation ◽  
Small Nucleolar Rnas ◽  
Primary Cells ◽  
Cell Proliferation And Differentiation ◽  
Cancerous Cell ◽  
Proliferation And Differentiation ◽  
Non Coding Rnas ◽  
Nucleolar Rnas

AbstractSmall nucleolar RNAs (snoRNAs) are non-coding RNAs conserved from archeobacteria to mammals. In humans, various snoRNAs have been associated with pathologies as well as with cancer. Recently in Drosophila, a new snoRNA named jouvence has been involved in lifespan. Since snoRNAs are well conserved through evolution, both structurally and functionally, jouvence orthologue has been identified in human, allowing hypothesizing that jouvence could display a similar function (increasing healthy lifespan) in human. Here, we report the characterization of the human snoRNA-jouvence, which was not yet annotated in the genome. We show, both in stably cancerous cell lines and in primary cells, that its overexpression stimulates the cell proliferation. In contrast, its knockdown, by siRNA leads to an opposite phenotype, a decrease in cell proliferation. Transcriptomic analysis reveals that overexpression of jouvence leads to a dedifferentiation signature of the cells, a cellular effect comparable to rejuvenation. Inversely, the knockdown of jouvence leads to a decrease of genes involved in ribosomes biogenesis and spliceosome in agreement with the canonical role of a H/ACA box snoRNA. In this context, jouvence could represent a now tool to fight against the deleterious effect of aging, as well as a new target in cancer therapy.

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 The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Paz Nombela ◽  
Borja Miguel-López ◽  
Sandra Blanco
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Therapeutic Potential ◽  
Biological Processes ◽  
Rna Modifications ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Function ◽  
Made In

AbstractRNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.

scholarly journals High-throughput identification of C/D box snoRNA targets with CLIP and RiboMeth-seq.

2016 ◽  
Author(s):  
Rafal Gumienny ◽  
Dominik Jedlinski ◽  
Georges Martin ◽  
Arnau Vina-Villaseca ◽  
Mihaela Zavolan
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Expression Patterns ◽  
Ribonucleoprotein Complexes ◽  
Short Rnas ◽  
Genome Wide ◽  
The Many ◽  
Nucleolar Rnas ◽  
Comprehensive Characterization

Identification of long and short RNAs, their processing and expression patterns have been greatly facilitated by high-throughput sequencing. Frequently, these RNAs act as guides for ribonucleoprotein complexes that regulate the expression or processing of target RNAs. However, to determine the targets of the many newly discovered regulatory RNAs in high-throughput remains a challenge. To globally assign guide small nucleolar RNAs to site of 2'-O-ribose methylation in human cells, we here developed novel computational methods for the analysis of data that was generated with protocols designed to capture direct small RNA-target interactions and to identify the sites of 2'-O-ribose methylation genome-wide. We thereby determined that many "orphan" snoRNAs appear to guide 2'-O-ribose methylation at sites that are targeted by other snoRNAs and that snoRNAs can be reliably captured in interaction with many mRNAs, in which a subsequent 2'-O-methylation cannot be detected. Our study provides a reliable approach to the comprehensive characterization of snoRNA-target interactions in species beyond those in which these interactions have been traditionally studied and contribute to the rapidly developing field of "epitranscriptomics".

Sign in / Sign up

Export Citation Format

Share Document