scholarly journals Characterizing RNA Pseudouridylation by Convolutional Neural Networks

2017 ◽  
Author(s):  
Xuan He ◽  
Sai Zhang ◽  
Yanqing Zhang ◽  
Tao Jiang ◽  
Jianyang Zeng
Keyword(s):  
Transcriptional Regulation ◽  
Rna Structure ◽  
Large Scale ◽  
Rna Stability ◽  
Rna Modification ◽  
Functional Roles ◽  
Learning Framework ◽  
Translation Fidelity ◽  
Validation Tests ◽  
Post Transcriptional Regulation

AbstractThe most prevalent post-transcriptional RNA modification, pseudouridine (Ψ), also known as the fifth ribonucleoside, is widespread in rRNAs, tRNAs, snRNAs, snoRNAs and mRNAs. Pseudouridines in RNAs are implicated in many aspects of post-transcriptional regulation, such as the maintenance of translation fidelity, control of RNA stability and stabilization of RNA structure. However, our understanding of the functions, mechanisms as well as precise distribution of pseudourdines (especially in mRNAs) still remains largely unclear. Though thousands of RNA pseudouridylation sites have been identified by high-throughput experimental techniques recently, the landscape of pseudouridines across the whole transcriptome has not yet been fully delineated. In this study, we present a highly effective model, called PULSE (PseudoUridyLation Sites Estimator), to predict novel Ψ sites from large-scale profiling data of pseudouridines and characterize the contextual sequence features of pseudouridylation. PULSE employs a deep learning framework, called convolutional neural network (CNN), which has been successfully and widely used for sequence pattern discovery in the literature. Our extensive validation tests demonstrated that PULSE can outperform conventional learning models and achieve high prediction accuracy, thus enabling us to further characterize the transcriptome-wide landscape of pseudouridine sites. Overall, PULSE can provide a useful tool to further investigate the functional roles of pseudouridylation in post-transcriptional regulation.

scholarly journals A Deep Boosting Based Approach for Capturing the Sequence Binding Preferences of RNA-Binding Proteins from High-Throughput CLIP-Seq Data

2016 ◽  
Author(s):  
Shuya Li ◽  
Fanghong Dong ◽  
Yuexin Wu ◽  
Sai Zhang ◽  
Chen Zhang ◽  
...  
Keyword(s):  
High Throughput ◽  
Large Scale ◽  
Binding Proteins ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
False Negative ◽  
Functional Roles ◽  
Potential Applications ◽  
Validation Tests

AbstractCharacterizing the binding behaviors of RNA-binding proteins (RBPs) is important for understanding their functional roles in gene expression regulation. However, current high-throughput experimental methods for identifying RBP targets, such as CLIP-seq and RNAcompete, usually suffer from the false positive and false negative issues. Here, we develop a deep boosting based machine learning approach, called DeBooster, to accurately model the binding sequence preferences and identify the corresponding binding targets of RBPs from CLIP-seq data. Comprehensive validation tests have shown that DeBooster can outperform other state-of-the-art approaches in predicting RBP targets and recover false negatives that are common in current CLIP-seq data. In addition, we have demonstrated several new potential applications of DeBooster in understanding the regulatory functions of RBPs, including the binding effects of the RNA helicase MOV10 on mRNA degradation, the influence of different binding behaviors of the ADAR proteins on RNA editing, as well as the antagonizing effect of RBP binding on miRNA repression. Moreover, DeBooster may provide an effective index to investigate the effect of pathogenic mutations in RBP binding sites, especially those related to splicing events. We expect that DeBooster will be widely applied to analyze large-scale CLIP-seq experimental data and can provide a practically useful tool for novel biological discoveries in understanding the regulatory mechanisms of RBPs.

scholarly journals Production and Application of Stable Isotope-Labeled Internal Standards for RNA Modification Analysis

Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 26 ◽  
Author(s):  
Kayla Borland ◽  
Jan Diesend ◽  
Taku Ito-Kureha ◽  
Vigo Heissmeyer ◽  
Christian Hammann ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Isotope Labeling ◽  
Rna Stability ◽  
Internal Standard ◽  
Modified Nucleosides ◽  
Rna Modification ◽  
Mouse Tissue ◽  
Rna Modifications ◽  
Internal Standards ◽  
Translation Fidelity

Post-transcriptional RNA modifications have been found to be present in a wide variety of organisms and in different types of RNA. Nucleoside modifications are interesting due to their already known roles in translation fidelity, enzyme recognition, disease progression, and RNA stability. In addition, the abundance of modified nucleosides fluctuates based on growth phase, external stress, or possibly other factors not yet explored. With modifications ever changing, a method to determine absolute quantities for multiple nucleoside modifications is required. Here, we report metabolic isotope labeling to produce isotopically labeled internal standards in bacteria and yeast. These can be used for the quantification of 26 different modified nucleosides. We explain in detail how these internal standards are produced and show their mass spectrometric characterization. We apply our internal standards and quantify the modification content of transfer RNA (tRNA) from bacteria and various eukaryotes. We can show that the origin of the internal standard has no impact on the quantification result. Furthermore, we use our internal standard for the quantification of modified nucleosides in mouse tissue messenger RNA (mRNA), where we find different modification profiles in liver and brain tissue.

scholarly journals Role of N6-Methyladenosine RNA Modification in Cardiovascular Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Dandan Song ◽  
Jianhua Hou ◽  
Junduo Wu ◽  
Junnan Wang
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Transcriptional Regulation ◽  
Recent Progress ◽  
Rna Modification ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Despite treatments being improved and many risk factors being identified, cardiovascular disease (CVD) is still a leading cause of mortality and disability worldwide. N6-methyladenosine (m6A) is the most common, abundant, and conserved internal modification in RNAs and plays an important role in the development of CVD. Many studies have shown that aabnormal m6A modifications of coding RNAs are involved in the development of CVD. In addition, non-coding RNAs (ncRNAs) exert post-transcriptional regulation in many diseases including CVD. Although ncRNAs have also been found to be modified by m6A, the studies on m6A modifications of ncRNAs in CVD are currently lacking. In this review, we summarized the recent progress in understanding m6A modifications in the context of coding RNAs and ncRNAs, as well as their regulatory roles in CVD.

scholarly journals The increasing diversity and complexity of the RNA-binding protein repertoire in plants

2020 ◽  
Vol 287 (1935) ◽  
pp. 20201397 ◽  
Author(s):  
C. Marondedze
Keyword(s):  
Stress Responses ◽  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Functional Roles ◽  
Binding Domains ◽  
Quantitative Studies ◽  
Current State ◽  
Rna Interaction ◽  
Post Transcriptional Regulation

Post-transcriptional regulation has far-reaching implications on the fate of RNAs. It is gaining increasing momentum as a critical component in adjusting global cellular transcript levels during development and in response to environmental stresses. In this process, RNA-binding proteins (RBPs) are indispensable chaperones that naturally bind RNA via one or multiple globular RNA-binding domains (RBDs) changing the function or fate of the bound RNAs. Despite the technical challenges faced in plants in large-scale studies, several hundreds of these RBPs have been discovered and elucidated globally over the past few years. Recent discoveries have more than doubled the number of proteins implicated in RNA interaction, including identification of RBPs lacking classical RBDs. This review will discuss these new emerging classes of RBPs, focusing on the current state of the RBP repertoire in Arabidopsis thaliana , including the diverse functional roles derived from quantitative studies implicating RBPs in abiotic stress responses. Notably, this review highlights that 836 RBPs are enriched as Arabidopsis RBPs while 1865 can be classified as candidate RBPs. The review will also outline outstanding areas within this field that require addressing to advance our understanding and potential biotechnological applications of RBPs.

scholarly journals Experimental reproducibility limits the correlation between mRNA and protein abundances in tumour proteomic profiles

2021 ◽  
Author(s):  
Swathi Ramachandra Upadhya ◽  
Colm Ryan
Keyword(s):  
Transcriptional Regulation ◽  
Measurement Error ◽  
Large Scale ◽  
Moderate Correlation ◽  
Substantial Fraction ◽  
High Reproducibility ◽  
Aggregate Protein ◽  
Post Transcriptional Regulation ◽  
Unexplained Variation

Large-scale studies of human proteomes have revealed only a moderate correlation between mRNA and protein abundances. It is unclear to what extent this moderate correlation reflects post-transcriptional regulation and to what extent it reflects measurement error. Here, by analysing replicate proteomic profiles of tumour samples, we show that there is considerable variation in the reproducibility of measurements of individual proteins. We show that proteins with more reproducible measurements tend to have higher mRNA-protein correlation, suggesting that a substantial fraction of the unexplained variation between mRNA and protein abundances may be attributed to limitations in the reproducibility of proteomic quantification. We find that proteins that have high reproducibility in one study tend to have high reproducibility in others and exploit this to develop an 'aggregate protein reproducibility' score. This score can explain a substantial amount of the variation in mRNA-protein correlation across multiple studies of both healthy and tumour samples.

scholarly journals Cytoplasmic deadenylation: regulation of mRNA fate

2010 ◽  
Vol 38 (6) ◽  
pp. 1531-1536 ◽  
Author(s):  
Katrin Wiederhold ◽  
Lori A. Passmore
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Mrna Stability ◽  
Regulation Of Gene Expression ◽  
The Other ◽  
Mrna Turnover ◽  
Functional Roles ◽  
Specific Mrnas ◽  
Post Transcriptional Regulation ◽  
Mrna Fate

The poly(A) tail of mRNA has an important influence on the dynamics of gene expression. On one hand, it promotes enhanced mRNA stability to allow production of the protein, even after inactivation of transcription. On the other hand, shortening of the poly(A) tail (deadenylation) slows down translation of the mRNA, or prevents it entirely, by inducing mRNA decay. Thus deadenylation plays a crucial role in the post-transcriptional regulation of gene expression, deciding the fate of individual mRNAs. It acts both in basal mRNA turnover, as well as in temporally and spatially regulated translation and decay of specific mRNAs. In the present paper, we discuss mRNA deadenylation in eukaryotes, focusing on the main deadenylase, the Ccr4–Not complex, including its composition, regulation and functional roles.

scholarly journals Novel insights into the pervasive role of RNA structure in post-transcriptional regulation of gene expression in plants

2021 ◽  
Vol 49 (4) ◽  
pp. 1829-1839
Author(s):  
Huakun Zhang ◽  
Yiliang Ding
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Rna Structure ◽  
Environmental Changes ◽  
Regulation Of Gene Expression ◽  
Intrinsic Property ◽  
Rna Degradation ◽  
Mrna Maturation ◽  
Recent Developments ◽  
Post Transcriptional Regulation

RNA folding is an intrinsic property of RNA that serves a key role in every step of post-transcriptional regulation of gene expression, from RNA maturation to translation in plants. Recent developments of genome-wide RNA structure profiling methods have transformed research in this area enabling focus to shift from individual molecules to the study of tens of thousands of RNAs. Here, we provide a comprehensive review of recent advances in the field. We discuss these new insights of RNA structure functionality within the context of post-transcriptional regulation including mRNA maturation, translation, and RNA degradation in plants. Notably, we also provide an overview of how plants exhibit different RNA structures in response to environmental changes.

scholarly journals RNA Granules: A View from the RNA Perspective

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3130 ◽  
Author(s):  
Siran Tian ◽  
Harrison A. Curnutte ◽  
Tatjana Trcek
Keyword(s):  
Transcriptional Regulation ◽  
Rna Structure ◽  
Transcriptional Control ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Special Issue ◽  
Rna Granules ◽  
Rna Biology ◽  
A Cell ◽  
Post Transcriptional Regulation

RNA granules are ubiquitous. Composed of RNA-binding proteins and RNAs, they provide functional compartmentalization within cells. They are inextricably linked with RNA biology and as such are often referred to as the hubs for post-transcriptional regulation. Much of the attention has been given to the proteins that form these condensates and thus many fundamental questions about the biology of RNA granules remain poorly understood: How and which RNAs enrich in RNA granules, how are transcripts regulated in them, and how do granule-enriched mRNAs shape the biology of a cell? In this review, we discuss the imaging, genetic, and biochemical data, which have revealed that some aspects of the RNA biology within granules are carried out by the RNA itself rather than the granule proteins. Interestingly, the RNA structure has emerged as an important feature in the post-transcriptional control of granule transcripts. This review is part of the Special Issue in the Frontiers in RNA structure in the journal Molecules.

scholarly journals RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins

2018 ◽  
Author(s):  
Jing Zhang ◽  
Jason Liu ◽  
Donghoon Lee ◽  
Jo-Jo Feng ◽  
Lucas Lochovsky ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Binding Sites ◽  
Rna Structure ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Network Centrality ◽  
Impact Score ◽  
Variant Prioritization ◽  
Post Transcriptional Regulation

AbstractRNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant-prioritization methods only focus on transcriptional regulation. Here, we integrate the portfolio of ENCODE-RBP experiments to develop RADAR, a variant-scoring framework. RADAR uses conservation, RNA structure, network centrality, and motifs to provide an overall impact score. Then it further incorporates tissue-specific inputs to highlight disease-specific variants. Our results demonstrate RADAR can successfully pinpoint variants, both somatic and germline, associated with RBP-function dysregulation, that cannot be found by most current prioritization methods, for example variants affecting splicing.

Sign in / Sign up

Export Citation Format

Share Document