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Nature Plants Sep 2022Poly(A) tail is a hallmark of eukaryotic messenger RNA and its length plays an essential role in regulating mRNA metabolism. However, a comprehensive resource for plant...
Poly(A) tail is a hallmark of eukaryotic messenger RNA and its length plays an essential role in regulating mRNA metabolism. However, a comprehensive resource for plant poly(A) tail length has yet to be established. Here, we applied a poly(A)-enrichment-free, nanopore-based method to profile full-length RNA with poly(A) tail information in plants. Our atlas contains over 120 million polyadenylated mRNA molecules from seven different tissues of Arabidopsis, as well as the shoot tissue of maize, soybean and rice. In most tissues, the size of plant poly(A) tails shows peaks at approximately 20 and 45 nucleotides, while the poly(A) tails in pollen exhibit a distinct pattern with strong peaks centred at 55 and 80 nucleotides. Moreover, poly(A) tail length is regulated in a gene-specific manner-mRNAs with short half-lives in general have long poly(A) tails, while mRNAs with long half-lives are featured with relatively short poly(A) tails that peak at ~45 nucleotides. Across species, poly(A) tails in the nucleus are almost twice as long as in the cytoplasm. Our comprehensive dataset lays the groundwork for future functional and evolutionary studies on poly(A) tail length regulation in plants.
Topics: Arabidopsis; Cytoplasm; Poly A; RNA, Messenger; RNA, Plant
PubMed: 35982302
DOI: 10.1038/s41477-022-01224-9 -
Bioinformatics (Oxford, England) Aug 2021Alternative polyadenylation (APA) has been widely recognized as a widespread mechanism modulated dynamically. Studies based on 3' end sequencing and/or RNA-seq have...
MOTIVATION
Alternative polyadenylation (APA) has been widely recognized as a widespread mechanism modulated dynamically. Studies based on 3' end sequencing and/or RNA-seq have profiled poly(A) sites in various species with diverse pipelines, yet no unified and easy-to-use toolkit is available for comprehensive APA analyses.
RESULTS
We developed an R package called movAPA for modeling and visualization of dynamics of alternative polyadenylation across biological samples. movAPA incorporates rich functions for preprocessing, annotation and statistical analyses of poly(A) sites, identification of poly(A) signals, profiling of APA dynamics and visualization. Particularly, seven metrics are provided for measuring the tissue-specificity or usages of APA sites across samples. Three methods are used for identifying 3' UTR shortening/lengthening events between conditions. APA site switching involving non-3' UTR polyadenylation can also be explored. Using poly(A) site data from rice and mouse sperm cells, we demonstrated the high scalability and flexibility of movAPA in profiling APA dynamics across tissues and single cells.
AVAILABILITY AND IMPLEMENTATION
https://github.com/BMILAB/movAPA.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
Topics: 3' Untranslated Regions; Animals; Mice; Oryza; Poly A; Polyadenylation; RNA-Seq; Software
PubMed: 33258917
DOI: 10.1093/bioinformatics/btaa997 -
Journal of Inorganic Biochemistry Dec 2022To further determine the factors that affect the binding properties of ruthenium(II) polypyridine complexes with RNA duplex and to find excellent RNA-binding agents, the...
To further determine the factors that affect the binding properties of ruthenium(II) polypyridine complexes with RNA duplex and to find excellent RNA-binding agents, the binding properties of ruthenium(II) complexes [Ru(phen)(7-OCH-dppz)] (Ru1, phen = 1,10-phenan- throline, 7-OCH-dppz = 7-methoxy-dipyrido-[3,2-a,2',3'-c]-phenazine) and [Ru(phen)(7-NO- dppz)] (Ru2, 7-NO-dppz = 7-nitro-dipyrido-[3,2-a,2',3'-c]-phenazine) with RNA poly(A)•poly(U) duplex have been investigated by spectroscopic methods and viscosity measurements in this work. The results show that complexes Ru1 and Ru2 bind to poly(A)•poly(U) through intercalation and the binding affinity between Ru2 and poly(A)•poly(U) is greater than that of Ru1. Thermal denaturation experiments suggest that both ruthenium(II) complexes exhibit a significant stabilizing effect on poly(A)•poly(U) duplex. Moreover, fluorescence emission spectra exhibit that, deviating from Ru2, Ru1 exhibits a "light switch" effect for poly(A)•poly(U). This effect can be observed by the naked eye under UV light and adjusted by pH, meaning that Ru1 may act as a reversible pH controlled molecular "light switch". The results obtained in this work will contribute to our understanding of the significant influence of the intercalative ligand substituent effect in the binding process of ruthenium(II) complexes with RNA duplex.
Topics: Poly A; Ruthenium; Nitrogen Dioxide; RNA; Phenazines
PubMed: 36115329
DOI: 10.1016/j.jinorgbio.2022.111991 -
Nature Communications Jun 2023Minimally invasive biodegradable implants with regeneration have been a frontier trend in clinic. Degeneration of nucleus pulposus (NP) is irreversible in most of spine...
Minimally invasive biodegradable implants with regeneration have been a frontier trend in clinic. Degeneration of nucleus pulposus (NP) is irreversible in most of spine diseases, and traditional spinal fusion or discectomy usually injure adjacent segments. Here, an innovative minimally invasive biodegradable NP scaffold with function regeneration inspired by cucumber tendril is developed using shape memory polymer poly(glycerol-dodecanoate) (PGD), whose mechanical property is controlled to the similar with human NP by adjusting synthetic parameters. The chemokine stromal cell-derived factor-1α (SDF-1α) is immobilized to the scaffold recruiting autologous stem cells from peripheral tissue, which has better ability of maintaining disc height, recruiting autologous stem cells, and inducing regeneration of NP in vivo compared to PGD without chemokine group and hydrogel groups significantly. It provides an innovative way to design minimally invasive implants with biodegradation and functional recovery, especially for irreversible tissue injury, including NP, cartilage and so on.
Topics: Humans; Glycerol; Nucleus Pulposus; Absorbable Implants; Biodegradation, Environmental; Poly A
PubMed: 37391454
DOI: 10.1038/s41467-023-39604-0 -
Bioinformatics (Oxford, England) Sep 2018Processing of transcripts at the 3'-end involves cleavage at a polyadenylation site followed by the addition of a poly(A)-tail. By selecting which site is cleaved, the...
MOTIVATION
Processing of transcripts at the 3'-end involves cleavage at a polyadenylation site followed by the addition of a poly(A)-tail. By selecting which site is cleaved, the process of alternative polyadenylation enables genes to produce transcript isoforms with different 3'-ends. To facilitate the identification and treatment of disease-causing mutations that affect polyadenylation and to understand the sequence determinants underlying this regulatory process, a computational model that can accurately predict polyadenylation patterns from genomic features is desirable.
RESULTS
Previous works have focused on identifying candidate polyadenylation sites and classifying tissue-specific sites. By training on how multiple sites in genes are competitively selected for polyadenylation from 3'-end sequencing data, we developed a deep learning model that can predict the tissue-specific strength of a polyadenylation site in the 3' untranslated region of the human genome given only its genomic sequence. We demonstrate the model's broad utility on multiple tasks, without any application-specific training. The model can be used to predict which polyadenylation site is more likely to be selected in genes with multiple sites. It can be used to scan the 3' untranslated region to find candidate polyadenylation sites. It can be used to classify the pathogenicity of variants near annotated polyadenylation sites in ClinVar. It can also be used to anticipate the effect of antisense oligonucleotide experiments to redirect polyadenylation. We provide analysis on how different features affect the model's predictive performance and a method to identify sensitive regions of the genome at the single-based resolution that can affect polyadenylation regulation.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
Topics: 3' Untranslated Regions; Gene Expression Regulation; Genome, Human; Genomics; Humans; Poly A; Polyadenylation
PubMed: 29648582
DOI: 10.1093/bioinformatics/bty211 -
BMC Genomics Aug 2017Polyadenylation is a critical stage of RNA processing during the formation of mature mRNA, and is present in most of the known eukaryote protein-coding transcripts and...
BACKGROUND
Polyadenylation is a critical stage of RNA processing during the formation of mature mRNA, and is present in most of the known eukaryote protein-coding transcripts and many long non-coding RNAs. The correct identification of poly(A) signals (PAS) not only helps to elucidate the 3'-end genomic boundaries of a transcribed DNA region and gene regulatory mechanisms but also gives insight into the multiple transcript isoforms resulting from alternative PAS. Although progress has been made in the in-silico prediction of genomic signals, the recognition of PAS in DNA genomic sequences remains a challenge.
RESULTS
In this study, we analyzed human genomic DNA sequences for the 12 most common PAS variants. Our analysis has identified a set of features that helps in the recognition of true PAS, which may be involved in the regulation of the polyadenylation process. The proposed features, in combination with a recognition model, resulted in a novel method and tool, Omni-PolyA. Omni-PolyA combines several machine learning techniques such as different classifiers in a tree-like decision structure and genetic algorithms for deriving a robust classification model. We performed a comparison between results obtained by state-of-the-art methods, deep neural networks, and Omni-PolyA. Results show that Omni-PolyA significantly reduced the average classification error rate by 35.37% in the prediction of the 12 considered PAS variants relative to the state-of-the-art results.
CONCLUSIONS
The results of our study demonstrate that Omni-PolyA is currently the most accurate model for the prediction of PAS in human and can serve as a useful complement to other PAS recognition methods. Omni-PolyA is publicly available as an online tool accessible at www.cbrc.kaust.edu.sa/omnipolya/ .
Topics: Data Mining; Genome, Human; Genomics; Humans; Poly A; Polyadenylation
PubMed: 28810905
DOI: 10.1186/s12864-017-4033-7 -
International Journal of Biological... Jul 2023Poly(3-hydroxybutyrate) (PHB) was blended with medium-chain-length PHAs (mcl-PHAs) for improving its flexibility while nanocellulose (NC) was added as a reinforcing...
Poly(3-hydroxybutyrate) (PHB) was blended with medium-chain-length PHAs (mcl-PHAs) for improving its flexibility while nanocellulose (NC) was added as a reinforcing agent. Even and odd-chain-length PHAs, having as main component poly(3-hydroxyoctanoate) (PHO) or poly(3-hydroxynonanoate) (PHN) were synthesized and served as PHB modifiers. The effects of PHO and PHN on the morphology, thermal, mechanical and biodegradation behaviors of PHB were different, especially in the presence of NC. The addition of mcl-PHAs decreased the storage modulus (E') of PHB blends by about 40 %. The further addition of NC mitigated this decrease bringing the E' of PHB/PHO/NC close to that of PHB and having a minor effect on the E' of PHB/PHN/NC. The biodegradability of PHB/PHN/NC was higher than that of PHB/PHO/NC, the latter's being close to that of neat PHB after soil burial for four months. The results showed a complex effect of NC, which enhanced the interaction between PHB and mcl-PHAs and decreased the size of PHO/PHN inclusions (1.9 ± 0.8/2.6 ± 0.9 μm) while increasing the accessibility of water and microorganisms during soil burial. The blown film extrusion test showed the ability of mcl-PHA and NC modified PHB to stretch forming uniform tube and supports the application of these biomaterials in the packaging sector.
Topics: Polyhydroxyalkanoates; 3-Hydroxybutyric Acid; Biocompatible Materials; Poly A; Nanocomposites; Polyesters
PubMed: 37307975
DOI: 10.1016/j.ijbiomac.2023.125324 -
International Journal of Biological... Jul 2023Poly (β-L-malic acid) (PMLA) is attracting industrial interest for its potential application in medicine and other industries, whose functions primarily depend upon its...
Poly (β-L-malic acid) (PMLA) is attracting industrial interest for its potential application in medicine and other industries, whose functions primarily depend upon its molecular size and chemical structure. Up to now, the fractionation and characterization of PMLA produced by Aureobasidium spp. were still unclear. In this study, the product from A. melanogenum ipe-1 was effectively fractionated using 300 and 50 kDa membranes. During the filtration, the mechanisms of membrane fouling were illegible since the PMLA can both reject and permeate the membrane, while the main fouling mechanism varied between standard blocking and complete blocking during the diafiltration. After fractionation, 14.0, 8.4 and 77.6 % of the PMLAs with Ms of 75,134, 21,344 and 10,056 Da were distributed in the 300 kDa retentate after diafiltrating, 50 kDa retentate after diafiltrating, and the 50 kDa permeate, respectively. The M/Ms of the PMLAs were 4.12, 1.92, and 1.12 in the three fractions. Based on characteristic spectra of NMR, HPLC and FTIR, the product was not usual L-malic acid monomers, but glucose-terminated PMLA. The glucose was located at the terminal hydroxyl of PMLA. These results would serve as a valuable guide for process design and practical operation in subsequent industrial application.
Topics: Aureobasidium; Polymers; Fermentation; Malates; Poly A
PubMed: 37182630
DOI: 10.1016/j.ijbiomac.2023.124720 -
International Journal of Biological... Dec 2022Crystallinity and flame retardancy are two key properties for poly(lactic acid)(PLA) in applications. In this paper, a quaternary phosphonium salt poly(ionic liquid)...
Crystallinity and flame retardancy are two key properties for poly(lactic acid)(PLA) in applications. In this paper, a quaternary phosphonium salt poly(ionic liquid) (PIL) and a phosphamide (POFA) were prepared. The PIL, POFA and their blend were used to regulate the flame retardancy and crystallization behaviors of PLA using the limiting oxygen index, UL-94 vertical burning, and thermogravimetric analysis, and differential scanning calorimetry etc. The results showed that a synergistic effect exists between PIL and POFA on flame retardancy. When 6 wt% PIL/POFA (2/1) was added into PLA, its LOI value is 28.0 vol%, and achieves the UL-94 V-0 rating while the PLA composites containing 6 wt% PIL or POFA just achieve the UL-94 V2. The PIL/POFA improves the flame retardancy of PLA by melting-away mode. In addition, the crystallization rate of PLA containing PIL/POFA is faster than that of PLA/PIL and PLA/POFA. The degradation of PLA induced by PIL/POFA produces some small molecular oligomers, which enhances the molecular chain mobility and rearrangement, thus contributes to better flame retardancy and faster crystallization.
Topics: Ionic Liquids; Crystallization; Polyesters; Dimethoate; Poly A
PubMed: 36370854
DOI: 10.1016/j.ijbiomac.2022.11.053 -
Methods in Molecular Biology (Clifton,... 2024The poly(A) tail is a sequence of several adenosine nucleotides added to the 3' end of RNA molecules transcribed by polymerase II. The dynamics of poly(A) tail length...
The poly(A) tail is a sequence of several adenosine nucleotides added to the 3' end of RNA molecules transcribed by polymerase II. The dynamics of poly(A) tail length play a significant role in regulating post-transcriptional gene expression by regulating the stability, translation, and decay of messenger RNAs. As a result, an accurate measurement of poly(A) tail length changes is important for understanding its regulatory function in different cellular contexts. Here, we outline a method for using nanopore sequencing and linear mixed models to analyze differences in poly(A) tail length across conditions.
Topics: Nanopore Sequencing; Nucleotidyltransferases; RNA, Messenger; Nucleotides; Poly A
PubMed: 37824076
DOI: 10.1007/978-1-0716-3481-3_16