scholarly journals The activity of human enhancers is modulated by the splicing of their associated lncRNAs

2022 ◽  
Vol 18 (1) ◽  
pp. e1009722
Author(s):  
Jennifer Yihong Tan ◽  
Ana Claudia Marques
Keyword(s):  
Genetic Factors ◽  
Gene Expression Regulation ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Enhancer Activity ◽  
Highly Active ◽  
Genome Wide ◽  
A Genome ◽  
Enhancer Function ◽  
Outstanding Question

Pervasive enhancer transcription is at the origin of more than half of all long noncoding RNAs in humans. Transcription of enhancer-associated long noncoding RNAs (elncRNA) contribute to their cognate enhancer activity and gene expression regulation in cis. Recently, splicing of elncRNAs was shown to be associated with elevated enhancer activity. However, whether splicing of elncRNA transcripts is a mere consequence of accessibility at highly active enhancers or if elncRNA splicing directly impacts enhancer function, remains unanswered. We analysed genetically driven changes in elncRNA splicing, in humans, to address this outstanding question. We showed that splicing related motifs within multi-exonic elncRNAs evolved under selective constraints during human evolution, suggesting the processing of these transcripts is unlikely to have resulted from transcription across spurious splice sites. Using a genome-wide and unbiased approach, we used nucleotide variants as independent genetic factors to directly assess the causal relationship that underpin elncRNA splicing and their cognate enhancer activity. We found that the splicing of most elncRNAs is associated with changes in chromatin signatures at cognate enhancers and target mRNA expression. We provide evidence that efficient and conserved processing of enhancer-associated elncRNAs contributes to enhancer activity.

scholarly journals The activity of human enhancers is modulated by the splicing of their associated lncRNAs

2020 ◽  
Author(s):  
Jennifer Y. Tan ◽  
Ana C. Marques
Keyword(s):  
Genetic Factors ◽  
Gene Expression Regulation ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Enhancer Activity ◽  
Highly Active ◽  
Genome Wide ◽  
A Genome ◽  
Enhancer Function ◽  
Outstanding Question

ABSTRACTPervasive enhancer transcription is at the origin of more than half of all long noncoding RNAs in humans. Transcription of enhancer-associated long noncoding RNAs (elncRNA) contribute to their cognate enhancer activity and gene expression regulation in cis. Recently, splicing of elncRNAs was shown to be associated with elevated enhancer activity. However, whether splicing of elncRNA transcripts is a mere consequence of accessibility at highly active enhancers or if elncRNA splicing directly impacts enhancer function, remains unanswered.We analysed genetically driven changes in elncRNA expression, in humans, to address this outstanding question. We showed that splicing related motifs within multi-exonic elncRNAs evolved under selective constraints during human evolution, suggesting the processing of these transcripts is unlikely to have resulted from transcription across spurious splice sites. Using a genome-wide and unbiased approach, we used nucleotide variants as independent genetic factors to directly assess the causal relationship that underpin elncRNA splicing and their cognate enhancer activity. We found that the splicing of most elncRNAs is associated with changes in chromatin signatures at cognate enhancers and target mRNA expression.We conclude that efficient and conserved processing of enhancer-associated elncRNAs contributes to enhancer activity.

scholarly journals Transcriptomic and Genome-wide Association Study Reveal Long Noncoding RNAs Responding to Nitrogen Deficiency in Maize

2020 ◽  
Author(s):  
PENG MA ◽  
Xiao Zhang ◽  
Bowen Luo ◽  
Zhen Chen ◽  
Xuan He ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Nitrogen Deficiency ◽  
Snp Array ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Genome Wide Association ◽  
Rna Seq ◽  
Genome Wide ◽  
A Genome

Abstract Background: Long noncoding RNAs (lncRNAs) play important roles in essential biological processes. However, our understanding of lncRNAs as competing endogenous RNAs (ceRNAs) and their responses to nitrogen stress is still limited.Results: Here, we surveyed the lncRNAs and miRNAs in maize inbred line P178 leaves and roots at the seedling stage under high-nitrogen and low-nitrogen conditions using lncRNA-Seq and small RNA-Seq. A total of 894 differentially expressed lncRNAs and 38 different miRNAs were identified. Co-expression analysis found two lncRNAs and four lncRNA-targets could competitively combine with ZmmiR159 and ZmmiR164, respectively. To dissect the genetic regulatory by which lncRNAs might enable adaptation to limited nitrogen availability. An association mapping panel containing a high-density single–nucleotide polymorphism (SNP) array (56,110 SNPs) combined with variable LN resistance-related phenotypes obtained from hydroponics was used for a genome-wide association study (GWAS). By combining GWAS and RNA-Seq, 170 differently expressed lncRNAs within the range of significant markers were screened. Moreover, 40 consistently LN-responsive genes including those involved in glutamine biosynthesis and nitrogen acquisition in root were identified. Transient expression assays in Nicotiana benthamiana demonstrated LNC_002923 could inhabit ZmmiR159-guided cleavage of Zm00001d015521. Conclusions: These lncRNAs containing trait-associated significant SNPs could consider to be related to root development and nutrient utilization. Taken together, the results of our study can provide new insights into the potential regulatory roles of lncRNAs in response to LN stress, and give valuable information for further screening of candidates as well as the improvement of maize regarding LN-responsive resistance.

Transcriptional enhancers: from prediction to functional assessment on a genome-wide scale

Genome ◽  
2020 ◽  
pp. 1-23
Author(s):  
Ian C. Tobias ◽  
Luis E. Abatti ◽  
Sakthi D. Moorthy ◽  
Shanelle Mullany ◽  
Tiegh Taylor ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Target Genes ◽  
Regulatory Sequences ◽  
Enhancer Activity ◽  
Reading Frame ◽  
Enhancer Prediction ◽  
Genome Wide ◽  
A Genome ◽  
Enhancer Function

Enhancers are cis-regulatory sequences located distally to target genes. These sequences consolidate developmental and environmental cues to coordinate gene expression in a tissue-specific manner. Enhancer function and tissue specificity depend on the expressed set of transcription factors, which recognize binding sites and recruit cofactors that regulate local chromatin organization and gene transcription. Unlike other genomic elements, enhancers are challenging to identify because they function independently of orientation, are often distant from their promoters, have poorly defined boundaries, and display no reading frame. In addition, there are no defined genetic or epigenetic features that are unambiguously associated with enhancer activity. Over recent years there have been developments in both empirical assays and computational methods for enhancer prediction. We review genome-wide tools, CRISPR advancements, and high-throughput screening approaches that have improved our ability to both observe and manipulate enhancers in vitro at the level of primary genetic sequences, chromatin states, and spatial interactions. We also highlight contemporary animal models and their importance to enhancer validation. Together, these experimental systems and techniques complement one another and broaden our understanding of enhancer function in development, evolution, and disease.

scholarly journals Transcriptomic and genome-wide association study reveal long noncoding RNAs responding to nitrogen deficiency in maize

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peng Ma ◽  
Xiao Zhang ◽  
Bowen Luo ◽  
Zhen Chen ◽  
Xuan He ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Nitrogen Deficiency ◽  
Snp Array ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Genome Wide Association ◽  
Rna Seq ◽  
Genome Wide ◽  
A Genome

Abstract Background Long noncoding RNAs (lncRNAs) play important roles in essential biological processes. However, our understanding of lncRNAs as competing endogenous RNAs (ceRNAs) and their responses to nitrogen stress is still limited. Results Here, we surveyed the lncRNAs and miRNAs in maize inbred line P178 leaves and roots at the seedling stage under high-nitrogen (HN) and low-nitrogen (LN) conditions using lncRNA-Seq and small RNA-Seq. A total of 894 differentially expressed lncRNAs and 38 different miRNAs were identified. Co-expression analysis found that two lncRNAs and four lncRNA-targets could competitively combine with ZmmiR159 and ZmmiR164, respectively. To dissect the genetic regulatory by which lncRNAs might enable adaptation to limited nitrogen availability, an association mapping panel containing a high-density single–nucleotide polymorphism (SNP) array (56,110 SNPs) combined with variable LN tolerant-related phenotypes obtained from hydroponics was used for a genome-wide association study (GWAS). By combining GWAS and RNA-Seq, 170 differently expressed lncRNAs within the range of significant markers were screened. Moreover, 40 consistently LN-responsive genes including those involved in glutamine biosynthesis and nitrogen acquisition in root were identified. Transient expression assays in Nicotiana benthamiana demonstrated that LNC_002923 could inhabit ZmmiR159-guided cleavage of Zm00001d015521. Conclusions These lncRNAs containing trait-associated significant SNPs could consider to be related to root development and nutrient utilization. Taken together, the results of our study can provide new insights into the potential regulatory roles of lncRNAs in response to LN stress, and give valuable information for further screening of candidates as well as the improvement of maize resistance to LN stress.

scholarly journals Genome-Wide Identification and Characterization of Long Noncoding RNAs Involved in Chinese Wheat Mosaic Virus Infection of Nicotiana benthamiana

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 232
Author(s):  
Weiran Zheng ◽  
Haichao Hu ◽  
Qisen Lu ◽  
Peng Jin ◽  
Linna Cai ◽  
...  
Keyword(s):  
Virus Infection ◽  
Mosaic Virus ◽  
Nicotiana Benthamiana ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Differentially Expressed ◽  
Genome Wide ◽  
Chinese Wheat

Recent studies have shown that a large number of long noncoding RNAs (lncRNAs) can regulate various biological processes in animals and plants. Although lncRNAs have been identified in many plants, they have not been reported in the model plant Nicotiana benthamiana. Particularly, the role of lncRNAs in plant virus infection remains unknown. In this study, we identified lncRNAs in N. benthamiana response to Chinese wheat mosaic virus (CWMV) infection by RNA sequencing. A total of 1175 lncRNAs, including 65 differentially expressed lncRNAs, were identified during CWMV infection. We then analyzed the functions of some of these differentially expressed lncRNAs. Interestingly, one differentially expressed lncRNA, XLOC_006393, was found to participate in CWMV infection as a precursor to microRNAs in N. benthamiana. These results suggest that lncRNAs play an important role in the regulatory network of N. benthamiana in response to CWMV infection.

scholarly journals Deep learning identifies genome-wide DNA binding sites of long noncoding RNAs

RNA Biology ◽  
2018 ◽  
Vol 15 (12) ◽  
pp. 1468-1476 ◽  
Author(s):  
Fan Wang ◽  
Pranik Chainani ◽  
Tommy White ◽  
Jin Yang ◽  
Yu Liu ◽  
...  
Keyword(s):  
Deep Learning ◽  
Dna Binding ◽  
Binding Sites ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Dna Binding Sites ◽  
Genome Wide
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