GENOMICS AND EPIGENOMICS IN MAIZE HYBRID KERNEL

The endosperm in cereals supplies nutrients to the developing kernel and seedling, and it is the primary tissue that gene imprinting occurs. Developing maize (Zea mays L.) endosperms were analysed for allelic gene expression in both reciprocal crosses of inbreds B73 and Mo17. A high-throughput transcriptome sequencing in kernels at 0, 3 up to 15 DAP of both reciprocals were performed, and found a gradual increased paternal transcript expression in 3 and 5 DAP kernels. Meanwhile, in 7 DAP endosperm, most of genes tested gave the ratio 2:1 maternal: paternal, suggesting that paternal genes are almost fully activated at 7 DAP. There were 300 PEGs and 499 MEGs identified across endosperm development stages. A 63 genes out of 116, 234 exhibited parent-specific expression were identified at 7, 10 and 15 DAP. Most of paternally expressed genes was at 7 DAP due to deviation of paternal alleles expression at this stage of development. Imprinted genes in terms of relative expression of maternal and paternal alleles differed at least five folds in both crosses. A total of 179 (1.6%) protein coding genes expressed in the endosperm were imprinted, 68 of them showed maternal preferential expression and 111 paternal expression, besides 38 long noncoding RNA were found imprinted and transcribed in either sense or antisense direction from intronic regions of normal protein coding genes or from intergenic regions. Imprinted genes showed clustering around the genome. A total of 21 imprinted genes in the maize hybrid endosperm had differentially methylated regions (DMRs). All DMRs were found to be hypomethylated in maternal alleles and hypermethylated in paternal alleles. These results confirm a complex mechanism controlling endosperm in maize in imprinting, auxin activity, and development regulation. Studying F2 kernels on F1 plants may shed a new light on controlling kernel number weight in unit of area.

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Comparative genomic analyses highlight the contribution of pseudogenized protein-coding genes to human lincRNAs

10.1101/163626 ◽

2017 ◽

Author(s):

Wan-Hsin Liu ◽

Zing Tsung-Yeh Tsai ◽

Huai-Kuang Tsai

Keyword(s):

Human Genome ◽

Noncoding Rna ◽

De Novo ◽

Systematic Investigation ◽

Comparative Genomic ◽

Protein Coding ◽

Protein Coding Genes ◽

Competing Endogenous Rnas ◽

Intergenic Regions ◽

The Relationship

AbstractBackgroundThe regulatory roles of long intergenic noncoding RNAs (lincRNAs) in humans have been revealed through the use of advanced sequencing technology. Recently, three possible scenarios of lincRNA origin have been proposed: de novo origination from intergenic regions, duplication from long noncoding RNA, and pseudogenization from protein. The first two scenarios are largely studied and supported, yet few studies focused on the evolution from pseudo genized protein-coding sequence to lincRNA. Due to the non-mutually exclusive nature that these three scenarios have, accompanied by the need of systematic investigation of lincRNA origination, we conduct a comparative genomics study to investigate the evolution of human lincRNAs.ResultsCombining with syntenic analysis and stringent Blastn e-value cutoff, we found that the majority of lincRNAs are aligned to the intergenic regions of other species. Interestingly, 193 human lincRNAs could have protein-coding orthologs in at least two of nine vertebrates. Transposable elements in these conserved regions in human genome are much less than expectation. Moreover, 19% of these lincRNAs have overlaps with or are close to pseudogenes in the human genome.ConclusionsWe suggest that a notable portion of lincRNAs could be derived from pseudogenized protein-coding genes. Furthermore, based on our computational analysis, we hypothesize that a subset of these lincRNAs could have potential to regulate their paralogs by functioning as competing endogenous RNAs. Our results provide evolutionary evidence of the relationship between human lincRNAs and protein-coding genes.

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Discovering long noncoding RNA predictors of anticancer drug sensitivity beyond protein-coding genes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1909998116 ◽

2019 ◽

Vol 116 (44) ◽

pp. 22020-22029 ◽

Cited By ~ 9

Author(s):

Aritro Nath ◽

Eunice Y. T. Lau ◽

Adam M. Lee ◽

Paul Geeleher ◽

William C. S. Cho ◽

...

Keyword(s):

Anticancer Drug ◽

Noncoding Rna ◽

Large Scale ◽

Drug Response ◽

Cancer Cell Line ◽

Systematic Evaluation ◽

Protein Coding ◽

Protein Coding Genes ◽

Clinical Biomarkers ◽

Response Predictors

Large-scale cancer cell line screens have identified thousands of protein-coding genes (PCGs) as biomarkers of anticancer drug response. However, systematic evaluation of long noncoding RNAs (lncRNAs) as pharmacogenomic biomarkers has so far proven challenging. Here, we study the contribution of lncRNAs as drug response predictors beyond spurious associations driven by correlations with proximal PCGs, tissue lineage, or established biomarkers. We show that, as a whole, the lncRNA transcriptome is equally potent as the PCG transcriptome at predicting response to hundreds of anticancer drugs. Analysis of individual lncRNAs transcripts associated with drug response reveals nearly half of the significant associations are in fact attributable to proximal cis-PCGs. However, adjusting for effects of cis-PCGs revealed significant lncRNAs that augment drug response predictions for most drugs, including those with well-established clinical biomarkers. In addition, we identify lncRNA-specific somatic alterations associated with drug response by adopting a statistical approach to determine lncRNAs carrying somatic mutations that undergo positive selection in cancer cells. Lastly, we experimentally demonstrate that 2 lncRNAs, EGFR-AS1 and MIR205HG, are functionally relevant predictors of anti-epidermal growth factor receptor (EGFR) drug response.

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Diversity and evolution of the emerging Pandoraviridae family

10.1101/230904 ◽

2017 ◽

Cited By ~ 1

Author(s):

Matthieu Legendre ◽

Elisabeth Fabre ◽

Olivier Poirot ◽

Sandra Jeudy ◽

Audrey Lartigue ◽

...

Keyword(s):

Comparative Genomics ◽

De Novo ◽

Gene Duplications ◽

Statistical Features ◽

Strong Component ◽

Protein Coding ◽

Protein Coding Genes ◽

Intergenic Regions ◽

Comparative Genomics Analysis ◽

Horizontal Transfers

AbstractWith DNA genomes up to 2.5 Mb packed in particles of bacterium-like shape and dimension, the first two Acanthamoeba-infectingPandoravirusesremained the most spectacular viruses since their description in 2013. Our isolation of three new strains from distant locations and environments allowed us to perform the first comparative genomics analysis of the emerging worldwide-distributed Pandoraviridae family. Thorough annotation of the genomes combining transcriptomic, proteomic, and bioinformatic analyses, led to the discovery of many non-coding transcripts while significantly reducing the former set of predicted protein-coding genes. We found that the Pandoraviridae exhibit an open pan genome, the enormous size of which is not adequately explained by gene duplications or horizontal transfers. As most of the strain specific genes have no extant homolog and exhibit statistical features comparable to intergenic regions, we suggests thatde novogene creation is a strong component in the evolution of the giant Pandoravirus genomes.

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Pandoravirus celtis illustrates the microevolution processes at work in the giant Pandoraviridae genomes

10.1101/500207 ◽

2018 ◽

Cited By ~ 1

Author(s):

Matthieu Legendre ◽

Jean-Marie Alempic ◽

Nadège Philippe ◽

Audrey Lartigue ◽

Sandra Jeudy ◽

...

Keyword(s):

De Novo ◽

Gene Repertoire ◽

Protein Coding ◽

Genomic Changes ◽

Coding Regions ◽

Protein Coding Genes ◽

Intergenic Regions ◽

Mere Existence ◽

Increasing Functions ◽

Similar Gene

AbstractWith genomes of up to 2.7 Mb propagated in µm-long oblong particles and initially predicted to encode more than 2000 proteins, members of the Pandoraviridae family display the most extreme features of the known viral world. The mere existence of such giant viruses raises fundamental questions about their origin and the processes governing their evolution. A previous analysis of six newly available isolates, independently confirmed by a study including 3 others, established that the Pandoraviridae pan-genome is open, meaning that each new strain exhibits protein-coding genes not previously identified in other family members. With an average increment of about 60 proteins, the gene repertoire shows no sign of reaching a limit and remains largely coding for proteins without recognizable homologs in other viruses or cells (ORFans). To explain these results, we proposed that most new protein-coding genes were created de novo, from pre-existing non-coding regions of the G+C rich pandoravirus genomes. The comparison of the gene content of a new isolate, P. celtis, closely related (96% identical genome) to the previously described P. quercus is now used to test this hypothesis by studying genomic changes in a microevolution range. Our results confirm that the differences between these two similar gene contents mostly consist of protein-coding genes without known homologs (ORFans), with statistical signatures close to that of intergenic regions. These newborn proteins are under slight negative selection, perhaps to maintain stable folds and prevent protein aggregation pending the eventual emergence of fitness-increasing functions. Our study also unraveled several insertion events mediated by a transposase of the hAT family, 3 copies of which are found in P. celtis and are presumably active. Members of the Pandoraviridae are presently the first viruses known to encode this type of transposase.

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On the discovery of ADRAM, an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

10.1101/2021.08.01.454607 ◽

2021 ◽

Author(s):

XIang Li ◽

Qiongyi Zhao ◽

Ziqi Wang ◽

Wei-Siang Liau ◽

Dean Basic ◽

...

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Large Population ◽

Regulation Of Gene Expression ◽

Fear Extinction ◽

Early Gene ◽

Protein Coding ◽

Protein Coding Genes ◽

Chaperone Protein ◽

The Brain

Long-noncoding RNA (lncRNA) comprise a new class of genes that have been assigned key roles in development and disease. Many lncRNAs are specifically transcribed in the brain where they regulate the expression of protein-coding genes that underpin neuronal function; however, their role in learning and memory remains largely unexplored. We used RNA Capture-Seq to identify a large population of lncRNAs that are expressed in the infralimbic cortex of adult male mice in response to fear-related learning, with 14.5% of these annotated in the GENCODE database as lncRNAs with no known function. We combined these data with cell-type-specific ATAC-seq on neurons that had been selectively activated by fear-extinction learning, and revealed 434 lncRNAs derived from enhancer regions in the vicinity of protein-coding genes. In particular, we discovered an experience-induced lncRNA called ADRAM that acts as both a scaffold and a combinatorial guide to recruit the brain-enriched chaperone protein 14-3-3 to the promoter of the memory-associated immediate early gene Nr4a2. This leads to the expulsion of histone deactylases 3 and 4, and the recruitment of the histone acetyltransferase creb binding protein, which drives learning-induced Nr4a2 expression. Knockdown of ADRAM disrupts this interaction, blocks the expression of Nr4a2, and ultimately impairs the formation of fear-extinction memory. This study expands the lexicon of experience-dependent lncRNA activity in the brain, highlights enhancer-derived RNAs (eRNAs) as key players in the epigenetic regulation of gene expression associated with fear extinction, and suggests eRNAs, such as ADRAM, may constitute viable targets in developing novel treatments for fear-related anxiety disorders.

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Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis

10.21203/rs.2.10525/v4 ◽

2020 ◽

Author(s):

Xiao Ma ◽

Shuangshuang Cen ◽

Luming Wang ◽

Chao Zhang ◽

Limin Wu ◽

...

Keyword(s):

Messenger Rna ◽

Target Genes ◽

Expression Profiles ◽

Differentially Expressed ◽

Integrated Analysis ◽

Pelodiscus Sinensis ◽

Specific Expression ◽

Protein Coding ◽

Reproductive Regulation ◽

Protein Coding Genes

Abstract Background: The gonad is the major factor affecting animal reproduction. The regulatory mechanism of the expression of protein-coding genes involved in reproduction still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction have been investigated in some species. However, the regulatory patterns of miRNA and lncRNA in the sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of Chinese soft-shelled turtle, Pelodiscus sinensis.Results: We identified 10 446 mature miRNAs, 20 414 mRNAs and 28 500 lncRNAs in the ovaries and testes, and 633 miRNAs, 11 319 mRNAs, and 10 495 lncRNAs showed differential expression. A total of 2 814 target genes were identified for miRNAs. The predicted target genes of these differentially expressed (DE) miRNAs and lncRNAs included abundant genes related to reproductive regulation. Furthermore, we found that 189 DEmiRNAs and 5 408 DElncRNAs showed sex-specific expression. Of these, 3 DEmiRNAs and 917 DElncRNAs were testis-specific, and 186 DEmiRNAs and 4 491 DElncRNAs were ovary-specific. We further constructed complete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 103 DEmiRNAs, 636 DEmRNAs, and 1 622 DElncRNAs. The target genes for the differentially expressed miRNAs and lncRNAs included abundant genes involved in gonadal development, including Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1.Conclusions: In animals, miRNA and lncRNA as master regulators regulate reproductive processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for studying the molecular processes involved in sexual reproduction and genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproductive traits for aquaculture.

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Bacterial Noncoding RNAs Excised from within Protein-Coding Transcripts

mBio ◽

10.1128/mbio.01730-18 ◽

2018 ◽

Vol 9 (5) ◽

Cited By ~ 14

Author(s):

Daniel Dar ◽

Rotem Sorek

Keyword(s):

Expression Patterns ◽

Noncoding Rnas ◽

Large Set ◽

Rna Structures ◽

Protein Coding ◽

Small Noncoding Rnas ◽

Coding Regions ◽

Protein Coding Genes ◽

Evolutionarily Conserved ◽

Intergenic Regions

ABSTRACT Prokaryotic genomes encode a plethora of small noncoding RNAs (ncRNAs) that fine-tune the expression of specific genes. The vast majority of known bacterial ncRNAs are encoded from within intergenic regions, where their expression is controlled by promoter and terminator elements, similarly to protein-coding genes. In addition, recent studies have shown that functional ncRNAs can also be derived from gene 3′ untranslated regions (3′UTRs) via an alternative biogenesis pathway, in which the ncRNA segment is separated from the mRNA via RNase cleavage. Here, we report the detection of a large set of decay-generated noncoding RNAs (decRNAs), many of which are completely embedded within protein-coding mRNA regions rather than in the UTRs. We show that these decRNAs are “carved out” of the mRNA through the action of RNase E and that they are predicted to fold into highly stable RNA structures, similar to those of known ncRNAs. A subset of these decRNAs is predicted to interact with Hfq or ProQ or both, which act as ncRNA chaperones, and some decRNAs display evolutionarily conserved sequences and conserved expression patterns between different species. These results suggest that mRNA protein-coding regions may harbor a large set of potentially functional small RNAs. IMPORTANCE Bacteria and archaea utilize regulatory small noncoding RNAs (ncRNAs) to control the expression of specific genetic programs. These ncRNAs are almost exclusively encoded within intergenic regions and are independently transcribed. Here, we report on a large set ncRNAs that are “carved out” from within the protein-coding regions of Escherichia coli mRNAs by cellular RNases. These protected mRNA fragments fold into energetically stable RNA structures, reminiscent of those of intergenic regulatory ncRNAs. In addition, a subset of these ncRNAs coprecipitate with the major ncRNA chaperones Hfq and ProQ and display evolutionarily conserved sequences and conserved expression patterns between different bacterial species. Our data suggest that protein-coding genes can potentially act as a reservoir of regulatory ncRNAs.

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Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis

10.21203/rs.2.10525/v1 ◽

2019 ◽

Author(s):

Xiao Ma ◽

Shuangshuang Cen ◽

Luming Wang ◽

Chao Zhang ◽

Limin Wu ◽

...

Keyword(s):

Messenger Rna ◽

Regulatory Networks ◽

Target Genes ◽

Expression Profiles ◽

Integrated Analysis ◽

Regulation Mechanism ◽

Pelodiscus Sinensis ◽

Specific Expression ◽

Protein Coding ◽

Protein Coding Genes

Abstract Abstract Background: Gonad is the major factor affecting the animal reproduction. The regulation mechanism of protein coding genes expression involved reproduction is still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction had been investigated in some species. However, the regulation patterns of miRNA and lncRNA in sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of the soft-shelled turtle, Pelodiscus sinensis. Results: We identified 10 796 mature miRNAs, 44 678 mRNAs, and 58 923 lncRNAs in the testis and ovary. A total of 16 817 target genes were identified for miRNAs. Of these, 11 319 mRNAs, 10 495 lncRNAs, and 633 miRNAs were expressed differently. The predicted target genes of these differential expression (DE) miRNAs and lncRNAs included genes related to reproduction regulation. Furthermore, we found that 5 408 DElncRNAs and 186 DE miRNAs showed sex-specific expression. Of these, 3 miRNAs and 917 lncRNAs were testis specific and 186 DEmiRNAs and 4 491 DElncRNAs were ovary specific. We constructed compete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 273 DEmRNAs, 5 730 DEmiRNAs, and 2 945 DElncRNAs. The target genes for the different expressed of miRNAs and lncRNAs included Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1, etc. Conclusions: In animals, miRNA and lncRNA regulate the reproduction process, including the regulation of oocyte maturation and spermatogenesis. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproduction traits for aquaculture.

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An integrative proteogenomics approach reveals peptides encoded by annotated lincRNA in the mouse kidney inner medulla

Physiological Genomics ◽

10.1152/physiolgenomics.00048.2020 ◽

2020 ◽

Vol 52 (10) ◽

pp. 485-491

Author(s):

Cameron T. Flower ◽

Lihe Chen ◽

Hyun Jun Jung ◽

Viswanathan Raghuram ◽

Mark A. Knepper ◽

...

Keyword(s):

Noncoding Rnas ◽

Peptide Identification ◽

Mouse Kidney ◽

Open Reading Frames ◽

Specific Expression ◽

Protein Coding ◽

Protein Coding Genes ◽

Peptide Database ◽

Liquid Chromatography Tandem Mass ◽

Spectrum Matching

Long noncoding RNAs (lncRNAs) are intracellular transcripts longer than 200 nucleotides and lack protein-coding information. A subclass of lncRNA known as long intergenic noncoding RNAs (lincRNAs) are transcribed from genomic regions that share no overlap with annotated protein-coding genes. Increasing evidence has shown that some annotated lincRNA transcripts do in fact contain open reading frames (ORFs) encoding functional short peptides in the cell. Few robust methods for lincRNA-encoded peptide identification have been reported, and the tissue-specific expression of these peptides has been largely unexplored. Here we propose an integrative workflow for lincRNA-encoded peptide discovery and test it on the mouse kidney inner medulla (IM). In brief, low molecular weight protein fractions were enriched from homogenate of IMs and trypsinized into shorter peptides, which were sequenced by high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). To curate a hypothetical lincRNA-encoded peptide database for peptide-spectrum matching following LC-MS/MS, we performed RNA-Seq on IMs, computationally removed reads overlapping with annotated protein-coding genes, and remapped the remaining reads to a database of mouse noncoding transcripts to infer lincRNA expression. Expressed lincRNAs were searched for ORFs by an existing rule-based algorithm, and translated ORFs were used for peptide-spectrum matching. Peptides identified by LC-MS/MS were further evaluated by using several quality control criteria and bioinformatics methods. We discovered three novel lincRNA-encoded peptides, which are conserved in mouse, rat, and human. The workflow can be adapted for discovery of small protein-coding genes in any species or tissue where noncoding transcriptome information is available.

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Protein coding genes as hosts for noncoding RNA expression

Seminars in Cell and Developmental Biology ◽

10.1016/j.semcdb.2017.08.016 ◽

2018 ◽

Vol 75 ◽

pp. 3-12 ◽

Cited By ~ 24

Author(s):

Vincent Boivin ◽

Gabrielle Deschamps-Francoeur ◽

Michelle S Scott

Keyword(s):

Noncoding Rna ◽

Rna Expression ◽

Protein Coding ◽

Protein Coding Genes

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