scholarly journals GC-AG Introns Features in Long Non-coding and Protein-Coding Genes Suggest Their Role in Gene Expression Regulation

2019 ◽  
Author(s):  
Monah Abou Alezz ◽  
Ludovica Celli ◽  
Giulia Belotti ◽  
Antonella Lisa ◽  
Silvia Bione
Keyword(s):  
Gene Expression Regulation ◽  
Expression Regulation ◽  
Splice Sites ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
First Intron ◽  
Genes Expression ◽  
Donor And Acceptor ◽  
Significant Enrichment ◽  
Splice Junctions

ABSTRACTLong non-coding RNAs (lncRNAs) are recognized as an important class of regulatory molecules involved in a variety of biological functions. However, the regulatory mechanisms of long non-coding genes expression are still poorly understood. The characterization of the genomic features of lncRNAs is crucial to get insight into their function. In this study, we exploited recent annotations by GENCODE to characterize the genomic and splicing features of long non-coding genes in comparison with protein-coding ones, both in human and mouse. Our analysis highlighted differences between the two classes of genes in terms of their gene architecture. Significant differences in the splice sites usage were observed between long non-coding and protein-coding genes (PCG). While the frequency of non-canonical GC-AG splice junctions represents about 0.8% of total splice sites in PCGs, we identified a significant enrichment of the GC-AG splice sites in long non-coding genes, both in human (3.0%) and mouse (1.9%). In addition, we found a positional bias of GC-AG splice sites being enriched in the first intron in both classes of genes. Moreover, a significant shorter length and weaker donor and acceptor sites were found comparing GC-AG introns to GT-AG introns. Genes containing at least one GC-AG intron were found conserved in many species, more prone to alternative splicing and a functional analysis pointed toward their enrichment in specific biological processes such as DNA repair. Our study shows for the first time that GC-AG introns are mainly associated with lncRNAs and are preferentially located in the first intron. Additionally, we discovered their regulatory potential indicating the existence of a new mechanism of non-coding and PCGs expression regulation.

scholarly journals GC-AG Introns Features in Long Non-coding and Protein-Coding Genes Suggest Their Role in Gene Expression Regulation

2020 ◽  
Vol 11 ◽  
Author(s):  
Monah Abou Alezz ◽  
Ludovica Celli ◽  
Giulia Belotti ◽  
Antonella Lisa ◽  
Silvia Bione
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Expression Regulation ◽  
Protein Coding ◽  
Protein Coding Genes

scholarly journals Open chromatin analysis in Trypanosoma cruzi life forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci

2021 ◽  
Author(s):  
Alex RJ Lima ◽  
Saloe B Poubel ◽  
Juliana N Roson ◽  
Loyze PO de Lima ◽  
Hellida M Costa-Silva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Trypanosoma Cruzi ◽  
Gene Expression Regulation ◽  
Gene Clusters ◽  
Expression Regulation ◽  
Open Chromatin ◽  
Protein Coding ◽  
Posttranscriptional Control ◽  
Protein Coding Genes ◽  
The Impact

Background: Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. Results: Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences in T. cruzi genome compartments, putative transcriptional start regions and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. Conclusion: Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.

scholarly journals Open Chromatin Analysis in Trypanosoma Cruzi Life Forms Highlights Critical Differences in Genomic Compartments and Developmental Regulation at tDNA Loci

2021 ◽  
Author(s):  
Alex RJ Lima ◽  
Saloe B Poubel ◽  
Juliana N Rosón ◽  
Loyze PO de Lima ◽  
Hellida M Costa-Silva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Trypanosoma Cruzi ◽  
Gene Expression Regulation ◽  
Gene Clusters ◽  
Expression Regulation ◽  
Open Chromatin ◽  
Protein Coding ◽  
Posttranscriptional Control ◽  
Protein Coding Genes ◽  
The Impact

Abstract Background: Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. Results: Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences in T. cruzi genome compartments, putative transcriptional start regions and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. Conclusion: Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.

scholarly journals LncExpDB: an expression database of human long non-coding RNAs

2020 ◽  
Vol 49 (D1) ◽  
pp. D962-D968 ◽  
Author(s):  
Zhao Li ◽  
Lin Liu ◽  
Shuai Jiang ◽  
Qianpeng Li ◽  
Changrui Feng ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Biological Functions ◽  
Protein Coding ◽  
Web Interfaces ◽  
Functional Studies ◽  
Protein Coding Genes ◽  
Genes Expression ◽  
Wide Range ◽  
Non Coding Rnas ◽  
User Friendly

Abstract Expression profiles of long non-coding RNAs (lncRNAs) across diverse biological conditions provide significant insights into their biological functions, interacting targets as well as transcriptional reliability. However, there lacks a comprehensive resource that systematically characterizes the expression landscape of human lncRNAs by integrating their expression profiles across a wide range of biological conditions. Here, we present LncExpDB (https://bigd.big.ac.cn/lncexpdb), an expression database of human lncRNAs that is devoted to providing comprehensive expression profiles of lncRNA genes, exploring their expression features and capacities, identifying featured genes with potentially important functions, and building interactions with protein-coding genes across various biological contexts/conditions. Based on comprehensive integration and stringent curation, LncExpDB currently houses expression profiles of 101 293 high-quality human lncRNA genes derived from 1977 samples of 337 biological conditions across nine biological contexts. Consequently, LncExpDB estimates lncRNA genes’ expression reliability and capacities, identifies 25 191 featured genes, and further obtains 28 443 865 lncRNA-mRNA interactions. Moreover, user-friendly web interfaces enable interactive visualization of expression profiles across various conditions and easy exploration of featured lncRNAs and their interacting partners in specific contexts. Collectively, LncExpDB features comprehensive integration and curation of lncRNA expression profiles and thus will serve as a fundamental resource for functional studies on human lncRNAs.

Long non-coding RNAs and splicing

2021 ◽  
Author(s):  
David Staněk
Keyword(s):  
Dominant Role ◽  
Splice Sites ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rna ◽  
Splicing Efficiency ◽  
Non Coding Rnas ◽  
Intron Removal ◽  
Long Non Coding Rna

Abstract In this review I focus on the role of splicing in long non-coding RNA (lncRNA) life. First, I summarize differences between the splicing efficiency of protein-coding genes and lncRNAs and discuss why non-coding RNAs are spliced less efficiently. In the second half of the review, I speculate why splice sites are the most conserved sequences in lncRNAs and what additional roles could splicing play in lncRNA metabolism. I discuss the hypothesis that the splicing machinery can, besides its dominant role in intron removal and exon joining, protect cells from undesired transcripts.

scholarly journals Conserved long-range RNA structures associated with pre-mRNA processing of human protein-coding genes

2020 ◽  
Author(s):  
Svetlana Kalmykova ◽  
Marina Kalinina ◽  
Stepan Denisov ◽  
Alexey Mironov ◽  
Dmitry Skvortsov ◽  
...  
Keyword(s):  
Long Range ◽  
Rna Folding ◽  
Current Knowledge ◽  
False Positive Rate ◽  
Human Protein ◽  
Circular Rnas ◽  
Splice Sites ◽  
Rna Structures ◽  
Protein Coding ◽  
Protein Coding Genes

AbstractThe ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. While DNA employs it for genome replication, RNA molecules fold into complicated secondary and tertiary structures. Current knowledge on functional RNA structures in human protein-coding genes is focused on locally-occurring base pairs. However, chemical crosslinking and proximity ligation experiments have demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved long-range RNA structures in the human transcriptome, which consists of 1.1 million pairs of conserved complementary regions (PCCRs). PCCRs tend to occur within introns proximally to splice sites, suppress intervening exons, circumscribe circular RNAs, and exert an obstructive effect on cryptic and inactive splice sites. The double-stranded structure of PCCRs is supported by a significant decrease of icSHAPE nucleotide accessibility, high abundance of A-to-I RNA editing sites, and frequent nearby occurrence of forked eCLIP peaks. Introns with PCCRs show a distinct splicing pattern in response to RNA Pol II slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. Additionally, transcript starts and ends are strongly enriched in regions between complementary parts of PCCRs, leading to an intriguing hypothesis that RNA folding coupled with splicing could mediate co-transcriptional suppression of premature cleavage and polyadenylation events. PCCR detection procedure is highly sensitive with respect to bona fide validated RNA structures at the expense of having a high false positive rate, which cannot be reduced without loss of sensitivity. The catalog of PCCRs is visualized through a UCSC Genome Browser track hub to facilitate further genome research on long-range RNA structures.

scholarly journals Antisense ncRNAs during early vertebrate development are divided in groups with distinct features

2020 ◽  
Author(s):  
Sanjana Pillay ◽  
Hazuki Takahashi ◽  
Piero Carninci ◽  
Aditi Kanhere
Keyword(s):  
Gene Expression Regulation ◽  
Expression Patterns ◽  
Vertebrate Development ◽  
Protein Coding ◽  
Antisense Rnas ◽  
Protein Coding Genes ◽  
Antisense Lncrnas ◽  
Group 2 ◽  
Group 1

ABSTRACTLong non-coding RNAs or lncRNAs are a broad class of non-protein coding RNAs that are >200nucleotides in length. A number of lncRNAs are shown to play an important role in gene expression regulation. LncRNAs antisense to a protein-coding gene can act either as positive or negative regulators of overlapping protein-coding mRNAs. Almost 50% of lncRNAs present during development of vertebrates such as zebrafish are of antisense lncRNA class. However, their role in gene expression regulation during development remains enigmatic. To understand the role of antisense lncRNAs in early vertebrate development, we took a computational biology approach to analyze existing as well as novel dataset. Our analysis of RNA sequencing data from zebrafish development indicates that antisense RNAs can be divided into two major classes based on their positive or negative co-expression patterns to the sense protein-coding genes. The ones with negative co-expression patterns or group-1 are maternal antisense lncRNAs that overlap mainly developmental genes. Group-2 with positive expression pattern overlap mainly house-keeping genes. Group-1 antisense lncRNAs are longer and more stable as compared to antisense lncRNAs in group-2. In addition, to answer if antisense RNAs in the two groups are differently localized in cell compartments, we deep-sequenced RNA from cytoplasmic and nuclear compartments during early developmental stages. The analysis of these compartment specific datasets revealed group-1 lncRNAs are cytosolic. Based on the cytosolic nature of group-1 RNAs and their higher complementarity to the overlapping developmental mRNAs, we speculate that the group-1 RNAs might function similar to microRNAs in silencing spurious expression of developmental genes. Group-1 and group-2 RNAs are also distinct in terms of their genomic configuration, conservation, length and transcriptional regulation. These results are not only important in understanding the role of antisense RNAs in development but also for predicting the nature of association between antisense lncRNA and overlapping protein-coding genes.

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