cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.19534854
title: Preferential translation of p53 target genes

description: The transcription factor p53 exerts its tumour suppressive effect through transcriptional activation of numerous target genes controlling cell cycle arrest, apoptosis, cellular senescence and DNA repair. In addition, there is evidence that p53 influences the translation of specific mRNAs, including translational inhibition of ribosomal protein synthesis and translational activation of MDM2. A challenge in the analysis of translational control is that changes in mRNA abundance exert a kinetic (passive) effect on ribosome densities. In order to separate these passive effects from active regulation of translation efficiency in response to p53 activation, we conducted a comprehensive analysis of translational regulation by comparative analysis of mRNA levels and ribosome densities upon DNA damage induced by neocarzinostatin in wild-type and TP53<sup>−/−</sup> HCT116 colorectal carcinoma cells. Thereby, we identified a specific group of mRNAs that are preferentially translated in response to p53 activation, many of which correspond to p53 target genes including MDM2, SESN1 and CDKN1A. By subsequent polysome profile analysis of SESN1 and CDKN1A mRNA, we could demonstrate that p53-dependent translational activation relies on a combination of inducing the expression of translationally advantageous isoforms and <i>trans</i>-acting mechanisms that further enhance the translation of these mRNAs.
DOI: 10.6084/m9.figshare.19932034
title: DARS-AS1 recruits METTL3/METTL14 to bind and enhance DARS mRNA m<sup>6</sup>A modification and translation for cytoprotective autophagy in cervical cancer

description: Cervical cancer (CC) is one of the most prevalent malignancies among females. Cytoprotective autophagy could confer cancer cell tolerance to hypoxic stress, promoting cell survival and adaptation. Aspartyl-tRNA synthetase 1 antisense 1 (DARS-AS1) is an oncogenic long non-coding RNA (lncRNA) in various cancers, but how DARS-AS1 regulates cytoprotective autophagy in hypoxic environment in CC remains unclear. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted to explore the interaction between hypoxia-inducible factor 1 subunit alpha (HIF1α) and DARS-AS1 promoter. Methylated RNA immunoprecipitation (MeRIP) followed by quantitative real-time polymerase-chain reaction (RT-qPCR) detected methylated RNA level. The process of autophagic maturation was monitored by immunofluorescence staining. Higher DARS-AS1 expression was found in CC tissues and cytoprotective. We also uncovered that hypoxic exposure induced cytoprotective autophagy via HIF1α/DARS-AS1/DARS axis. Moreover, DARS-AS1 was validated to facilitate DARS translation via recruiting N6-adenosine-methyltransferase methyltransferase like 3 (METTL3) and methyltransferase like 14 (METTL14), which bound with DARS mRNA DARS mRNA 5’ untranslated region (5ʹUTR) and promoting its translation. The present study demonstrated that the ‘HIF1α/DARS-AS1/DARS/ATG5/ATG3’ pathway regulated the hypoxia-induced cytoprotective autophagy of CC and might be a promising target of therapeutic strategies for patients afflicted with CC.
DOI: 10.6084/m9.figshare.19932034.v2
title: DARS-AS1 recruits METTL3/METTL14 to bind and enhance DARS mRNA m<sup>6</sup>A modification and translation for cytoprotective autophagy in cervical cancer

description: Cervical cancer (CC) is one of the most prevalent malignancies among females. Cytoprotective autophagy could confer cancer cell tolerance to hypoxic stress, promoting cell survival and adaptation. Aspartyl-tRNA synthetase 1 antisense 1 (DARS-AS1) is an oncogenic long non-coding RNA (lncRNA) in various cancers, but how DARS-AS1 regulates cytoprotective autophagy in hypoxic environment in CC remains unclear. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted to explore the interaction between hypoxia-inducible factor 1 subunit alpha (HIF1α) and DARS-AS1 promoter. Methylated RNA immunoprecipitation (MeRIP) followed by quantitative real-time polymerase-chain reaction (RT-qPCR) detected methylated RNA level. The process of autophagic maturation was monitored by immunofluorescence staining. Higher DARS-AS1 expression was found in CC tissues and cytoprotective. We also uncovered that hypoxic exposure induced cytoprotective autophagy via HIF1α/DARS-AS1/DARS axis. Moreover, DARS-AS1 was validated to facilitate DARS translation via recruiting N6-adenosine-methyltransferase methyltransferase like 3 (METTL3) and methyltransferase like 14 (METTL14), which bound with DARS mRNA DARS mRNA 5’ untranslated region (5ʹUTR) and promoting its translation. The present study demonstrated that the ‘HIF1α/DARS-AS1/DARS/ATG5/ATG3’ pathway regulated the hypoxia-induced cytoprotective autophagy of CC and might be a promising target of therapeutic strategies for patients afflicted with CC.
DOI: 10.6084/m9.figshare.19932034.v1
title: DARS-AS1 recruits METTL3/METTL14 to bind and enhance DARS mRNA m<sup>6</sup>A modification and translation for cytoprotective autophagy in cervical cancer

description: Cervical cancer (CC) is one of the most prevalent malignancies among females. Cytoprotective autophagy could confer cancer cell tolerance to hypoxic stress, promoting cell survival and adaptation. Aspartyl-tRNA synthetase 1 antisense 1 (DARS-AS1) is an oncogenic long non-coding RNA (lncRNA) in various cancers, but how DARS-AS1 regulates cytoprotective autophagy in hypoxic environment in CC remains unclear. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted to explore the interaction between hypoxia-inducible factor 1 subunit alpha (HIF1α) and DARS-AS1 promoter. Methylated RNA immunoprecipitation (MeRIP) followed by quantitative real-time polymerase-chain reaction (RT-qPCR) detected methylated RNA level. The process of autophagic maturation was monitored by immunofluorescence staining. Higher DARS-AS1 expression was found in CC tissues and cytoprotective. We also uncovered that hypoxic exposure induced cytoprotective autophagy via HIF1α/DARS-AS1/DARS axis. Moreover, DARS-AS1 was validated to facilitate DARS translation via recruiting N6-adenosine-methyltransferase methyltransferase like 3 (METTL3) and methyltransferase like 14 (METTL14), which bound with DARS mRNA DARS mRNA 5’ untranslated region (5ʹUTR) and promoting its translation. The present study demonstrated that the ‘HIF1α/DARS-AS1/DARS/ATG5/ATG3’ pathway regulated the hypoxia-induced cytoprotective autophagy of CC and might be a promising target of therapeutic strategies for patients afflicted with CC.
DOI: 10.6084/m9.figshare.21571055
title: On the predictibility of A-minor motifs from their local contexts

description: This study investigates the importance of the structural context in the formation of a type I/II A-minor motif. This very frequent structural motif has been shown to be important in the spatial folding of RNA molecules. We developed an automated method to classify A-minor motif occurrences according to their 3D context similarities, and we used a graph approach to represent both the structural A-minor motif occurrences and their classes at different scales. This approach leads us to uncover new subclasses of A-minor motif occurrences according to their local 3D similarities. The majority of classes are composed of homologous occurrences, but some of them are composed of non-homologous occurrences. The different classifications we obtain allow us to better understand the importance of the context in the formation of A-minor motifs. In a second step, we investigate how much knowledge of the context around an A-minor motif can help to infer its presence (and position). More specifically, we want to determine what kind of information, contained in the structural context, can be useful to characterize and predict A-minor motifs. We show that, for some A-minor motifs, the topology combined with a sequence signal is sufficient to predict the presence and the position of an A-minor motif occurrence. In most other cases, these signals are not sufficient for predicting the A-minor motif, however we show that they are good signals for this purpose. All the classification and prediction pipelines rely on automated processes, for which we describe the underlying algorithms and parameters.
DOI: 10.6084/m9.figshare.21571055.v1
title: On the predictibility of A-minor motifs from their local contexts

description: This study investigates the importance of the structural context in the formation of a type I/II A-minor motif. This very frequent structural motif has been shown to be important in the spatial folding of RNA molecules. We developed an automated method to classify A-minor motif occurrences according to their 3D context similarities, and we used a graph approach to represent both the structural A-minor motif occurrences and their classes at different scales. This approach leads us to uncover new subclasses of A-minor motif occurrences according to their local 3D similarities. The majority of classes are composed of homologous occurrences, but some of them are composed of non-homologous occurrences. The different classifications we obtain allow us to better understand the importance of the context in the formation of A-minor motifs. In a second step, we investigate how much knowledge of the context around an A-minor motif can help to infer its presence (and position). More specifically, we want to determine what kind of information, contained in the structural context, can be useful to characterize and predict A-minor motifs. We show that, for some A-minor motifs, the topology combined with a sequence signal is sufficient to predict the presence and the position of an A-minor motif occurrence. In most other cases, these signals are not sufficient for predicting the A-minor motif, however we show that they are good signals for this purpose. All the classification and prediction pipelines rely on automated processes, for which we describe the underlying algorithms and parameters.
DOI: 10.6084/m9.figshare.19501872
title: A positive feedback loop between LINC01605 and NF-κB pathway promotes tumor growth in nasopharyngeal carcinoma

description: zong non-coding RNAs (lncRNAs) have been identified as crucial effector in modulating the progression of assorted malignancies. In our study, the main aim was to unveil the role and the underlying regulatory mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in nasopharyngeal carcinoma (NPC). RT-qPCR analysis results suggested that LINC01605 was upregulated in NPC cells. According to the results of function experiments, LINC01605 promoted NPC cell proliferation and impeded cell apoptosis. The oncogenic role of LINC01605 in NPC was further validated by animal experiments. Additionally, we verified that LINC01605 regulated Ikbkb expression to promote the nuclear translocation of p65 and thereby activated the NF-κB pathway in NPC cells. Mechanism experiments further suggested that LINC01605 could regulate Ikbkb expression via sponging miR-942-5p. Moreover, LINC01605 recruited IGF2BP2 to stabilize ubiquitin-specific protease 3 (USP3) mRNA and thereby enhanced the stability of IkB subunit beta (IKKβ) protein. In addition, p65 acted as a transcription activator to upregulate LINC01605 in NPC cells. In conclusion, this study demonstrated a positive feedback loop between LINC01605 and the NF-κB signalling pathway that promoted NPC cell growth, thus providing new insights to better understand NPC.
DOI: 10.6084/m9.figshare.19501872.v1
title: A positive feedback loop between LINC01605 and NF-κB pathway promotes tumor growth in nasopharyngeal carcinoma

description: zong non-coding RNAs (lncRNAs) have been identified as crucial effector in modulating the progression of assorted malignancies. In our study, the main aim was to unveil the role and the underlying regulatory mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in nasopharyngeal carcinoma (NPC). RT-qPCR analysis results suggested that LINC01605 was upregulated in NPC cells. According to the results of function experiments, LINC01605 promoted NPC cell proliferation and impeded cell apoptosis. The oncogenic role of LINC01605 in NPC was further validated by animal experiments. Additionally, we verified that LINC01605 regulated Ikbkb expression to promote the nuclear translocation of p65 and thereby activated the NF-κB pathway in NPC cells. Mechanism experiments further suggested that LINC01605 could regulate Ikbkb expression via sponging miR-942-5p. Moreover, LINC01605 recruited IGF2BP2 to stabilize ubiquitin-specific protease 3 (USP3) mRNA and thereby enhanced the stability of IkB subunit beta (IKKβ) protein. In addition, p65 acted as a transcription activator to upregulate LINC01605 in NPC cells. In conclusion, this study demonstrated a positive feedback loop between LINC01605 and the NF-κB signalling pathway that promoted NPC cell growth, thus providing new insights to better understand NPC.
DOI: 10.6084/m9.figshare.25458841
title: RefEx2 Datasets for Human FANTOM5

description: RefEx2 is a project to collect, organize, and curate transcriptome datasets of various species as reference resources for gene expression data analysis. It provides 6 reference datasets for four different species: humans, mice, Drosophila melanogaster, and Arabidopsis thaliana. This directory contains the following datasets on human FANTOM5:220428_fantom5_human_refextable_sample_stats.tsv.gzProcessed data matrixfantom5_hg38_refextable_grouped_sample_desc.tsvGrouped sample descriptionfantom5_hg38_refextable_sampleID_mapping.tsvSample ID mappingsHuman_FANTOM5_p1p2_refined_original_sample_annotation.tsvOriginal sample annotations provided by the FANTOM5 project, modified in part by RefEx2.No. of genes: 21,035<br>No. of samples: 863<br>Key ID: NCBI geneOriginal data: https://fantom.gsc.riken.jp/5/data/<br>Reference(s): DOI: 10.1038/sdata.2017.112, DOI: 10.1093/nar/gkaa1054Processing procedures: GitHub
DOI: 10.6084/m9.figshare.25458841.v1
title: RefEx2 Datasets for Human FANTOM5

description: RefEx2 is a project to collect, organize, and curate transcriptome datasets of various species as reference resources for gene expression data analysis. It provides 6 reference datasets for four different species: humans, mice, Drosophila melanogaster, and Arabidopsis thaliana. This directory contains the following datasets on human FANTOM5:220428_fantom5_human_refextable_sample_stats.tsv.gzProcessed data matrixfantom5_hg38_refextable_grouped_sample_desc.tsvGrouped sample descriptionfantom5_hg38_refextable_sampleID_mapping.tsvSample ID mappingsHuman_FANTOM5_p1p2_refined_original_sample_annotation.tsvOriginal sample annotations provided by the FANTOM5 project, modified in part by RefEx2.No. of genes: 21,035<br>No. of samples: 863<br>Key ID: NCBI geneOriginal data: https://fantom.gsc.riken.jp/5/data/<br>Reference(s): DOI: 10.1038/sdata.2017.112, DOI: 10.1093/nar/gkaa1054Processing procedures: GitHub
DOI: 10.6084/m9.figshare.17704063.v1
title: piRNAQuest V.2: an updated resource for searching through the piRNAome of multiple species

description: PIWI interacting RNAs (piRNAs) have emerged as important gene regulators in recent times. Since the release of our first version of piRNAQuest in 2014, lots of novel piRNAs have been annotated in different species other than human, mouse and rat. Such new developments in piRNA research have led us to develop an updated database piRNAQuest V.2. It consists of 92,77,689 piRNA entries for 25 new species of different phylum along with human, mouse and rat. Besides providing primary piRNA features which include their genomic location, with further information on piRNAs overlapping with repeat elements, pseudogenes and syntenic regions, etc., the novel features of this version includes (i) density based cluster prediction, (ii) piRNA expression profile across various healthy and disease systems and (iii) piRNA target prediction. The concept of density-based piRNA cluster identification is robust as it does not consider parametric distribution in its model. The piRNA expression profile for 21 disease systems including cancer have been hosted in addition to 32 tissue specific piRNA expression profile for various species. Further, the piRNA target prediction section includes both predicted and curated piRNA targets within eight disease systems and developmental stages of mouse testis. Further, users can visualize the piRNA-target duplex structure and the ping-pong signature pattern for all the ping-pong piRNA partners in different species. Overall, piRNAQuest V.2 is an updated user-friendly database which will serve as a useful resource to survey, search and retrieve information on piRNAs for multiple species. This freely accessible database is available at http://dibresources.jcbose.ac.in/zhumur/pirnaquest2.
DOI: 10.6084/m9.figshare.17704063
title: piRNAQuest V.2: an updated resource for searching through the piRNAome of multiple species

description: PIWI interacting RNAs (piRNAs) have emerged as important gene regulators in recent times. Since the release of our first version of piRNAQuest in 2014, lots of novel piRNAs have been annotated in different species other than human, mouse and rat. Such new developments in piRNA research have led us to develop an updated database piRNAQuest V.2. It consists of 92,77,689 piRNA entries for 25 new species of different phylum along with human, mouse and rat. Besides providing primary piRNA features which include their genomic location, with further information on piRNAs overlapping with repeat elements, pseudogenes and syntenic regions, etc., the novel features of this version includes (i) density based cluster prediction, (ii) piRNA expression profile across various healthy and disease systems and (iii) piRNA target prediction. The concept of density-based piRNA cluster identification is robust as it does not consider parametric distribution in its model. The piRNA expression profile for 21 disease systems including cancer have been hosted in addition to 32 tissue specific piRNA expression profile for various species. Further, the piRNA target prediction section includes both predicted and curated piRNA targets within eight disease systems and developmental stages of mouse testis. Further, users can visualize the piRNA-target duplex structure and the ping-pong signature pattern for all the ping-pong piRNA partners in different species. Overall, piRNAQuest V.2 is an updated user-friendly database which will serve as a useful resource to survey, search and retrieve information on piRNAs for multiple species. This freely accessible database is available at http://dibresources.jcbose.ac.in/zhumur/pirnaquest2.
DOI: 10.6084/m9.figshare.21406753
title: PRKCE non-coding variants influence on transcription as well as translation of its gene

description: Untranslated regions of the gene play a crucial role in gene expression regulation at mRNA and protein levels. Mutations at UTRs impact expression by altering transcription factor binding, transcriptional/translational efficacy, miRNA-mediated gene regulation, mRNA secondary structure, ribosomal translocation, and stability. PKCε, a serine/threonine kinase, is aberrantly expressed in numerous diseases such as cardiovascular disorders, neurological disorders, and cancers; its probable cause is unknown. Therefore, in the current study, the influence of PRKCE 5’-and 3'UTR variants was explored for their potential impact on its transcription and translation through several bioinformatics approaches. UTR variants data was obtained through different databases and initially evaluated for their regulatory function. Variants with regulatory function were then studied for their effect on PRKCE binding with transcription factors (TF) and miRNAs, as well as their impact on mRNA secondary structure. Study outcomes indicated the regulatory function of 73 5'UTR and 17 3'UTR variants out of 376. 5'UTR variants introduced AP1 binding sites and promoted the PRKCE transcription. Four 3'UTR variants introduced a circular secondary structure, increasing PRKCE translational efficacy. A region in 5'UTR position 45,651,564 to 45,651,644 was found where variants readily influenced the miRNA-PRKCE mRNA binding. The study further highlighted a PKCε-regulated feedback loop mechanism that induces the activity of TFs, promoting its gene transcription. The study provides foundations for experimentation to understand these variants’ role in diseases. These variants can also serve as the genetic markers for different diseases’ diagnoses after validation at the cell and population levels.
DOI: 10.6084/m9.figshare.21406753.v1
title: PRKCE non-coding variants influence on transcription as well as translation of its gene

description: Untranslated regions of the gene play a crucial role in gene expression regulation at mRNA and protein levels. Mutations at UTRs impact expression by altering transcription factor binding, transcriptional/translational efficacy, miRNA-mediated gene regulation, mRNA secondary structure, ribosomal translocation, and stability. PKCε, a serine/threonine kinase, is aberrantly expressed in numerous diseases such as cardiovascular disorders, neurological disorders, and cancers; its probable cause is unknown. Therefore, in the current study, the influence of PRKCE 5’-and 3'UTR variants was explored for their potential impact on its transcription and translation through several bioinformatics approaches. UTR variants data was obtained through different databases and initially evaluated for their regulatory function. Variants with regulatory function were then studied for their effect on PRKCE binding with transcription factors (TF) and miRNAs, as well as their impact on mRNA secondary structure. Study outcomes indicated the regulatory function of 73 5'UTR and 17 3'UTR variants out of 376. 5'UTR variants introduced AP1 binding sites and promoted the PRKCE transcription. Four 3'UTR variants introduced a circular secondary structure, increasing PRKCE translational efficacy. A region in 5'UTR position 45,651,564 to 45,651,644 was found where variants readily influenced the miRNA-PRKCE mRNA binding. The study further highlighted a PKCε-regulated feedback loop mechanism that induces the activity of TFs, promoting its gene transcription. The study provides foundations for experimentation to understand these variants’ role in diseases. These variants can also serve as the genetic markers for different diseases’ diagnoses after validation at the cell and population levels.
DOI: 10.6084/m9.figshare.19245933
title: A novel role for nucleolin in splice site selection

description: Latent 5ʹ splice sites, not normally used, are highly abundant in human introns, but are activated under stress and in cancer, generating thousands of nonsense mRNAs. A previously proposed mechanism to suppress latent splicing was shown to be independent of NMD, with a pivotal role for initiator-tRNA independent of protein translation. To further elucidate this mechanism, we searched for nuclear proteins directly bound to initiator-tRNA. Starting with UV-crosslinking, we identified nucleolin (NCL) interacting directly and specifically with initiator-tRNA in the nucleus, but not in the cytoplasm. Next, we show the association of initiator-tRNA and NCL with pre-mRNA. We further show that recovery of suppression of latent splicing by initiator-tRNA complementation is NCL dependent. Finally, upon nucleolin knockdown we show activation of latent splicing in hundreds of coding transcripts having important cellular functions. We thus propose nucleolin, a component of the endogenous spliceosome, through its direct binding to initiator-tRNA and its effect on latent splicing, as the first protein of a nuclear quality control mechanism regulating splice site selection to protect cells from latent splicing that can generate defective mRNAs.