Identification of 11 candidate structured noncoding RNA motifs in humans by comparative genomics

Abstract Background Only 1.5% of the human genome encodes proteins, while large part of the remaining encodes noncoding RNAs (ncRNA). Many ncRNAs form structures and perform many important functions. Accurately identifying structured ncRNAs in the human genome and discovering their biological functions remain a major challenge. Results Here, we have established a pipeline (CM-line) with the following features for analyzing the large genomes of humans and other animals. First, we selected species with larger genetic distances to facilitate the discovery of covariations and compatible mutations. Second, we used CMfinder, which can generate useful alignments even with low sequence conservation. Third, we removed repetitive sequences and known structured ncRNAs to reduce the workload of CMfinder. Fourth, we used Infernal to find more representatives and refine the structure. We reported 11 classes of structured ncRNA candidates with significant covariations in humans. Functional analysis showed that these ncRNAs may have variable functions. Some may regulate circadian clock genes through poly (A) signals (PAS); some may regulate the elongation factor (EEF1A) and the T-cell receptor signaling pathway by cooperating with RNA binding proteins. Conclusions By searching for important features of RNA structure from large genomes, the CM-line has revealed the existence of a variety of novel structured ncRNAs. Functional analysis suggests that some newly discovered ncRNA motifs may have biological functions. The pipeline we have established for the discovery of structured ncRNAs and the identification of their functions can also be applied to analyze other large genomes.

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Identification of 11 candidate structured noncoding RNA motifs in humans by comparative genomics

10.21203/rs.3.rs-118997/v1 ◽

2020 ◽

Author(s):

Lijuan Hou ◽

Jin Xie ◽

Yaoyao Wu ◽

Jiaojiao Wang ◽

Anqi Duan ◽

...

Keyword(s):

Functional Analysis ◽

Human Genome ◽

Noncoding Rna ◽

Rna Binding ◽

Clock Genes ◽

Rna Binding Proteins ◽

Repetitive Sequences ◽

Cell Receptor ◽

Biological Functions ◽

Large Genomes

Abstract Background Only 1.5% of the human genome encodes proteins, while most of the remaining encodes noncoding RNAs (ncRNA). Many ncRNAs form structures and perform many important functions. Accurately identifying structured ncRNAs in the human genome and discovering their biological functions remain a major challenge. Results Here, we have established a pipeline (CM-line) with the following features for analyzing the large genomes of humans and other animals. First, we selected species with larger genetic distances to facilitate the discovery of covariations and compatible mutations. Second, we used CMfinder, which can generate useful alignments even with low sequence conservation. Third, we removed repetitive sequences and known structured ncRNAs to reduce the workload of CMfinder. Fourth, we used Infernal to find more representatives and refine the structure. We reported 11 classes of structured ncRNA candidates with significant covariations in humans. Functional analysis showed that these ncRNAs have variable functions. Some may regulate circadian clock genes through poly (A) signals (PAS); some may regulate the elongation factor (EEF1A) and the T-cell receptor signaling pathway by cooperating with RNA binding proteins. Conclusions By searching for important features of RNA structure from large genomes, the CM-line has revealed the existence of a variety of novel structured ncRNAs. Functional analysis provides evidence for the potential biological functions of some newly found ncRNA motifs. The pipeline we have established for the discovery of structured ncRNAs and the identification of their functions can also be applied to analyze other large genomes.

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A comprehensive review of circRNA: from purification and identification to disease marker potential

PeerJ ◽

10.7717/peerj.5503 ◽

2018 ◽

Vol 6 ◽

pp. e5503 ◽

Cited By ~ 31

Author(s):

Sheng Xu ◽

LuYu Zhou ◽

Murugavel Ponnusamy ◽

LiXia Zhang ◽

YanHan Dong ◽

...

Keyword(s):

Noncoding Rna ◽

High Stability ◽

Rna Binding ◽

Rna Binding Proteins ◽

Neurological Diseases ◽

Circular Rna ◽

Biological Functions ◽

Disease Marker ◽

Pathological Conditions ◽

Microrna Sponge

Circular RNA (circRNA) is an endogenous noncoding RNA with a covalently closed cyclic structure. Based on their components, circRNAs are divided into exonic circRNAs, intronic circRNAs, and exon-intron circRNAs. CircRNAs have well-conserved sequences and often have high stability due to their resistance to exonucleases. Depending on their sequence, circRNAs are involved in different biological functions, including microRNA sponge activity, modulation of alternative splicing or transcription, interaction with RNA-binding proteins, and rolling translation, and are a derivative of pseudogenes. CircRNAs are involved in the development of a variety of pathological conditions, such as cardiovascular diseases, diabetes, neurological diseases, and cancer. Emerging evidence has shown that circRNAs are likely to be new potential clinical diagnostic markers or treatments for many diseases. Here we describe circRNA research methods and biological functions, and discuss the potential relationship between circRNAs and disease progression.

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A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells

10.1101/033423 ◽

2015 ◽

Cited By ~ 1

Author(s):

Ailone Tichon ◽

Noa Gil ◽

Yoav Lubelsky ◽

Tal Havkin Solomon ◽

Doron Lemze ◽

...

Keyword(s):

Cell Division ◽

Human Genome ◽

Chromosome Segregation ◽

Binding Sites ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Rna Binding ◽

Rna Binding Proteins ◽

Mrna Levels ◽

Pumilio Proteins

AbstractThousands of long noncoding RNA (lncRNA) genes are encoded in the human genome, and hundreds of them are evolutionary conserved, but their functions and modes of action remain largely obscure. Particularly enigmatic lncRNAs are those that are exported to the cytoplasm, including NORAD – an abundant and highly conserved cytoplasmic lncRNA. Most of the sequence of NORAD is comprised of repetitive units that together contain at least 17 functional binding sites for the two Pumilio homologs in mammals. Through binding to PUM1 and PUM2, NORAD modulates the mRNA levels of their targets, which are enriched for genes involved in chromosome segregation during cell division. Our results suggest that some cytoplasmic lncRNAs function by modulating the activities of RNA binding proteins, an activity which positions them at key junctions of cellular signaling pathways.

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The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

Current Gene Therapy ◽

10.2174/1566523219666190716092203 ◽

2019 ◽

Vol 19 (4) ◽

pp. 255-263 ◽

Cited By ~ 13

Author(s):

Yuangang Wu ◽

Xiaoxi Lu ◽

Bin Shen ◽

Yi Zeng

Keyword(s):

Gene Expression ◽

Gene Therapy ◽

Extracellular Matrix ◽

Inflammatory Reaction ◽

Noncoding Rna ◽

Rna Binding ◽

Rna Binding Proteins ◽

Protein Translation ◽

Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

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CSBPI_Site：Multi-Information Sources of Features to RNA Binding Sites Prediction

Current Bioinformatics ◽

10.2174/1574893615666210108093950 ◽

2021 ◽

Vol 15 ◽

Author(s):

Lichao Zhang ◽

Zihong Huang ◽

Liang Kong

Keyword(s):

Computational Model ◽

Binding Sites ◽

Noncoding Rna ◽

Computational Models ◽

Information Sources ◽

Rna Binding ◽

Rna Binding Proteins ◽

Gradient Boosting ◽

Position Information ◽

Rna Binding Sites

Background: RNA-binding proteins establish posttranscriptional gene regulation by coordinating the maturation, editing, transport, stability, and translation of cellular RNAs. The immunoprecipitation experiments could identify interaction between RNA and proteins, but they are limited due to the experimental environment and material. Therefore, it is essential to construct computational models to identify the function sites. Objective: Although some computational methods have been proposed to predict RNA binding sites, the accuracy could be further improved. Moreover, it is necessary to construct a dataset with more samples to design a reliable model. Here we present a computational model based on multi-information sources to identify RNA binding sites. Method: We construct an accurate computational model named CSBPI_Site, based on xtreme gradient boosting. The specifically designed 15-dimensional feature vector captures four types of information (chemical shift, chemical bond, chemical properties and position information). Results: The satisfied accuracy of 0.86 and AUC of 0.89 were obtained by leave-one-out cross validation. Meanwhile, the accuracies were slightly different (range from 0.83 to 0.85) among three classifiers algorithm, which showed the novel features are stable and fit to multiple classifiers. These results showed that the proposed method is effective and robust for noncoding RNA binding sites identification. Conclusion: Our method based on multi-information sources is effective to represent the binding sites information among ncRNAs. The satisfied prediction results of Diels-Alder riboz-yme based on CSBPI_Site indicates that our model is valuable to identify the function site.

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Unique Archaeal Small RNAs

Annual Review of Genetics ◽

10.1146/annurev-genet-120417-031300 ◽

2018 ◽

Vol 52 (1) ◽

pp. 465-487 ◽

Cited By ~ 3

Author(s):

José Vicente Gomes-Filho ◽

Michael Daume ◽

Lennart Randau

Keyword(s):

Noncoding Rna ◽

Genome Rearrangement ◽

Rna Binding ◽

Elevated Temperatures ◽

Rna Binding Proteins ◽

Current Knowledge ◽

Extreme Environments ◽

Noncoding Rnas ◽

Hyperthermophilic Archaea ◽

Rna Modification

Advances in genome-wide sequence technologies allow for detailed insights into the complexity of RNA landscapes of organisms from all three domains of life. Recent analyses of archaeal transcriptomes identified interaction and regulation networks of noncoding RNAs in this understudied domain. Here, we review current knowledge of small, noncoding RNAs with important functions for the archaeal lifestyle, which often requires adaptation to extreme environments. One focus is RNA metabolism at elevated temperatures in hyperthermophilic archaea, which reveals elevated amounts of RNA-guided RNA modification and virus defense strategies. Genome rearrangement events result in unique fragmentation patterns of noncoding RNA genes that require elaborate maturation pathways to yield functional transcripts. RNA-binding proteins, e.g., L7Ae and LSm, are important for many posttranscriptional control functions of RNA molecules in archaeal cells. We also discuss recent insights into the regulatory potential of their noncoding RNA partners.

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Structural basis for recognition of human 7SK long noncoding RNA by the La-related protein Larp7

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1806276115 ◽

2018 ◽

Vol 115 (28) ◽

pp. E6457-E6466 ◽

Cited By ~ 20

Author(s):

Catherine D. Eichhorn ◽

Yuan Yang ◽

Lucas Repeta ◽

Juli Feigon

Keyword(s):

Noncoding Rna ◽

Rna Binding ◽

Rna Binding Proteins ◽

Transcription Elongation ◽

Structural Basis ◽

Titration Calorimetry ◽

Rna Recognition Motif ◽

Related Protein ◽

Binding Interface ◽

And Function

The La and the La-related protein (LARP) superfamily is a diverse class of RNA binding proteins involved in RNA processing, folding, and function. Larp7 binds to the abundant long noncoding 7SK RNA and is required for 7SK ribonucleoprotein (RNP) assembly and function. The 7SK RNP sequesters a pool of the positive transcription elongation factor b (P-TEFb) in an inactive state; on release, P-TEFb phosphorylates RNA Polymerase II to stimulate transcription elongation. Despite its essential role in transcription, limited structural information is available for the 7SK RNP, particularly for protein–RNA interactions. Larp7 contains an N-terminal La module that binds UUU-3′OH and a C-terminal atypical RNA recognition motif (xRRM) required for specific binding to 7SK and P-TEFb assembly. Deletion of the xRRM is linked to gastric cancer in humans. We report the 2.2-Å X-ray crystal structure of the human La-related protein group 7 (hLarp7) xRRM bound to the 7SK stem-loop 4, revealing a unique binding interface. Contributions of observed interactions to binding affinity were investigated by mutagenesis and isothermal titration calorimetry. NMR 13C spin relaxation data and comparison of free xRRM, RNA, and xRRM–RNA structures show that the xRRM is preordered to bind a flexible loop 4. Combining structures of the hLarp7 La module and the xRRM–7SK complex presented here, we propose a structural model for Larp7 binding to the 7SK 3′ end and mechanism for 7SK RNP assembly. This work provides insight into how this domain contributes to 7SK recognition and assembly of the core 7SK RNP.

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HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade

Cell Death and Disease ◽

10.1038/s41419-020-02738-w ◽

2020 ◽

Vol 11 (7) ◽

Cited By ~ 1

Author(s):

Jessica Rea ◽

Valentina Menci ◽

Paolo Tollis ◽

Tiziana Santini ◽

Alexandros Armaos ◽

...

Keyword(s):

Neuronal Differentiation ◽

Cell Fate ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Regulatory Networks ◽

Rna Binding ◽

Rna Binding Proteins ◽

Regulatory Cascade ◽

Expression Control ◽

Gene Expression Control

Abstract Neuronal differentiation is a timely and spatially regulated process, relying on precisely orchestrated gene expression control. The sequential activation/repression of genes driving cell fate specification is achieved by complex regulatory networks, where transcription factors and noncoding RNAs work in a coordinated manner. Herein, we identify the long noncoding RNA HOTAIRM1 (HOXA Transcript Antisense RNA, Myeloid-Specific 1) as a new player in neuronal differentiation. We demonstrate that the neuronal-enriched HOTAIRM1 isoform epigenetically controls the expression of the proneural transcription factor NEUROGENIN 2 that is key to neuronal fate commitment and critical for brain development. We also show that HOTAIRM1 activity impacts on NEUROGENIN 2 downstream regulatory cascade, thus contributing to the achievement of proper neuronal differentiation timing. Finally, we identify the RNA-binding proteins HNRNPK and FUS as regulators of HOTAIRM1 biogenesis and metabolism. Our findings uncover a new regulatory layer underlying NEUROGENIN 2 transitory expression in neuronal differentiation and reveal a previously unidentified function for the neuronal-induced long noncoding RNA HOTAIRM1.

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The Regulatory Functions of Circular RNAs in Digestive System Cancers

Cancers ◽

10.3390/cancers12030770 ◽

2020 ◽

Vol 12 (3) ◽

pp. 770 ◽

Cited By ~ 4

Author(s):

Xiao Yuan ◽

Ya Yuan ◽

Zhi He ◽

Diyan Li ◽

Bo Zeng ◽

...

Keyword(s):

Digestive System ◽

Rna Binding ◽

Rna Binding Proteins ◽

Circular Rna ◽

Research Progress ◽

Circular Rnas ◽

Biological Functions ◽

Ribonucleic Acids ◽

Mirna Sponges ◽

And Biological Markers

Circular ribonucleic acids (circRNAs), which are a type of covalently closed circular RNA, are receiving increasing attention. An increasing amount of evidence suggests that circRNAs are involved in the biogenesis and development of multiple diseases such as digestive system cancers. Dysregulated circRNAs have been found to act as oncogenes or tumour suppressors in digestive system cancers. Moreover, circRNAs are related to ageing and a wide variety of processes in tumour cells, such as cell apoptosis, invasion, migration, and proliferation. Moreover, circRNAs can perform a remarkable multitude of biological functions, such as regulating splicing or transcription, binding RNA-binding proteins to enable function, acting as microRNA (miRNA) sponges, and undergoing translated into proteins. However, in digestive system cancers, circRNAs function mainly as miRNA sponges. Herein, we summarise the latest research progress on biological functions of circRNAs in digestive system cancers. This review serves as a synopsis of potential therapeutic targets and biological markers for digestive system cancer.

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