Integration of multi-omics data of a genome-reduced bacterium: Prevalence of post-transcriptional regulation and its correlation with protein abundances

Wei-Hua Chen; Vera van Noort; Maria Lluch-Senar; Marco L. Hennrich; Judith A. H. Wodke; Eva Yus; Andreu Alibés; Guglielmo Roma; Daniel R. Mende; Christina Pesavento; Athanasios Typas; Anne-Claude Gavin; Luis Serrano; Peer Bork

doi:10.1093/nar/gkw004

PSDX: A Comprehensive Multi-Omics Association Database of Populus trichocarpa With a Focus on the Secondary Growth in Response to Stresses

Frontiers in Plant Science ◽

10.3389/fpls.2021.655565 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huiyuan Wang ◽

Sheng Liu ◽

Xiufang Dai ◽

Yongkang Yang ◽

Yunjun Luo ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Transcription Initiation ◽

High Throughput Sequencing ◽

Rna Binding ◽

Rna Binding Proteins ◽

Populus Trichocarpa ◽

Secondary Growth ◽

A Genome ◽

Post Transcriptional Regulation

Populus trichocarpa (P. trichocarpa) is a model tree for the investigation of wood formation. In recent years, researchers have generated a large number of high-throughput sequencing data in P. trichocarpa. However, no comprehensive database that provides multi-omics associations for the investigation of secondary growth in response to diverse stresses has been reported. Therefore, we developed a public repository that presents comprehensive measurements of gene expression and post-transcriptional regulation by integrating 144 RNA-Seq, 33 ChIP-seq, and six single-molecule real-time (SMRT) isoform sequencing (Iso-seq) libraries prepared from tissues subjected to different stresses. All the samples from different studies were analyzed to obtain gene expression, co-expression network, and differentially expressed genes (DEG) using unified parameters, which allowed comparison of results from different studies and treatments. In addition to gene expression, we also identified and deposited pre-processed data about alternative splicing (AS), alternative polyadenylation (APA) and alternative transcription initiation (ATI). The post-transcriptional regulation, differential expression, and co-expression network datasets were integrated into a new P. trichocarpa Stem Differentiating Xylem (PSDX) database, which further highlights gene families of RNA-binding proteins and stress-related genes. The PSDX also provides tools for data query, visualization, a genome browser, and the BLAST option for sequence-based query. Much of the data is also available for bulk download. The availability of PSDX contributes to the research related to the secondary growth in response to stresses in P. trichocarpa, which will provide new insights that can be useful for the improvement of stress tolerance in woody plants.

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The expression of the acarbose biosynthesis gene cluster in Actinoplanes sp. SE50/110 is dependent on the growth phase

10.21203/rs.3.rs-41287/v2 ◽

2021 ◽

Author(s):

Julian Droste ◽

Vera Ortseifen ◽

Lena Schaffert ◽

Marcus Persicke ◽

Susanne Schneiker-Bekel ◽

...

Keyword(s):

Transcriptional Regulation ◽

Stationary Phase ◽

Gene Cluster ◽

Growth Phase ◽

Formation Rate ◽

High Temporal Resolution ◽

Biosynthesis Gene Cluster ◽

Metabolic Switch ◽

A Genome ◽

Post Transcriptional Regulation

Abstract Background: Actinoplanes sp. SE50/110 is the natural producer of the diabetes mellitus drug acarbose, which is highly produced during the growth phase and ceases during the stationary phase. In previous works, the growth-dependency of acarbose formation was assumed to be caused by a decreasing transcription of the acarbose biosynthesis genes during transition and stationary growth phase. Results: In this study, transcriptomic data using RNA-seq and state-of-the-art proteomic data from seven time points of controlled bioreactor cultivations were used to analyze expression dynamics during growth of Actinoplanes sp. SE50/110. A hierarchical cluster analysis revealed co-regulated genes, which display similar transcription dynamics over the cultivation time. Aside from an expected metabolic switch from primary to secondary metabolism during transition phase, we observed a continuously decreasing transcript abundance of all acarbose biosynthetic genes from the early growth phase until stationary phase, with the strongest decrease for the monocistronically transcribed genes acbA, acbB, acbD and acbE. Our data confirm a similar trend for acb gene transcription and acarbose formation rate. Surprisingly, the proteome dynamics does not follow the respective transcription for all acb genes. This suggests different protein stabilities or post-transcriptional regulation of the Acb proteins, which in turn could indicate bottlenecks in the acarbose biosynthesis. Furthermore, several genes are co-expressed with the acb gene cluster over the course of the cultivation, including eleven transcriptional regulators (e.g. ACSP50_0424), two sigma factors (ACSP50_0644, ACSP50_6006) and further genes, which have not previously been in focus of acarbose research in Actinoplanes sp. SE50/110. Conclusion: In conclusion, we have demonstrated, that a genome wide transcriptome and proteome analysis in a high temporal resolution is well suited to study the acarbose biosynthesis and the transcriptional and post-transcriptional regulation thereof.

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A post-transcriptional regulatory code for mRNA stability during the zebrafish maternal-to-zygotic transition

10.1101/292441 ◽

2018 ◽

Author(s):

Charles E. Vejnar ◽

Mario Abdel Messih ◽

Carter M. Takacs ◽

Valeria Yartseva ◽

Panos Oikonomou ◽

...

Keyword(s):

Transcriptional Regulation ◽

Mrna Stability ◽

Binding Proteins ◽

Regulatory Elements ◽

Dependent Manner ◽

A Genome ◽

Maternal To Zygotic Transition ◽

Post Transcriptional Regulation ◽

Genome Activation

AbstractPost-transcriptional regulation is crucial to shape gene expression. During the Maternal-to-Zygotic Transition (MZT), thousands of maternal transcripts are regulated upon fertilization and genome activation. Transcript stability can be influenced by cis-elements and trans-factors, but how these inputs are integrated to determine the overall mRNA stability is unclear. Here, we show that most transcripts are under combinatorial regulation by multiple decay pathways during zebrafish MZT. To identify cis-regulatory elements, we performed a massively parallel reporter assay for stability-influencing sequences, which revealed that 3’-UTR poly-U motifs are associated with mRNA stability. In contrast, miR-430 target sequences, UAUUUAUU AU-rich elements (ARE), CCUC and CUGC elements emerged as the main destabilizing motifs in the embryo, with miR-430 and AREs causing mRNA deadenylation in a genome activation-dependent manner. To identify the trans-factors interacting with these cis-elements, we comprehensively profiled RNA-protein interactions and their associated regulatory activities across the transcriptome during the MZT. We find that poly-U binding proteins are preferentially associated with 3’-UTR sequences and stabilizing motifs, and that antagonistic sequence contexts for poly-C and poly-U binding proteins shape the binding landscape and magnitude of regulation across the transcriptome. Finally, we integrate these regulatory motifs into a machine learning model that accurately predicts the stability of mRNA reporters in vivo. Our findings reveal how mechanisms of post-transcriptional regulation are coordinated to direct changes in mRNA stability within the early zebrafish embryo.

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The expression of the acarbose biosynthesis gene cluster in Actinoplanes sp. SE50/110 is dependent on the growth phase

10.21203/rs.3.rs-41287/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Julian Droste ◽

Vera Ortseifen ◽

Lena Schaffert ◽

Marcus Persicke ◽

Susanne Schneiker-Bekel ◽

...

Keyword(s):

Transcriptional Regulation ◽

Gene Cluster ◽

Growth Phase ◽

Proteome Analysis ◽

Hierarchical Cluster ◽

High Temporal Resolution ◽

Biosynthesis Gene Cluster ◽

Metabolic Switch ◽

A Genome ◽

Post Transcriptional Regulation

Abstract Background: Actinoplanes sp. SE50/110 is the natural producer of the diabetes mellitus drug acarbose, which is highly produced during the growth phase and ceases during the stationary phase. In previous works, the growth-dependency of acarbose formation was assumed to be caused by a decreasing transcription of the acarbose biosynthesis genes during transition and stationary growth phase.Results: In this study, transcriptomic data using RNA-seq and state-of-the-art proteomic data from seven time points of controlled bioreactor cultivations were used to analyze expression dynamics during growth of Actinoplanes sp. SE50/110. A hierarchical cluster analysis revealed co-regulated genes, which display similar transcription dynamics over the cultivation time. Aside from the expected metabolic switch from primary to secondary metabolism during transition phase, we observed a significantly decreasing transcript abundance of all acarbose biosynthetic genes, with the strongest decrease for the monocistronically transcribed genes acbA, acbB, acbD and acbE. Our data confirm a similar trend for acb gene transcription and acarbose formation rate.Surprisingly, the proteome dynamics does not follow the respective transcription for all acb genes. This suggests different protein stabilities or post-transcriptional regulation of the Acb proteins, which in turn could indicate bottlenecks in the acarbose biosynthesis. Furthermore, several genes are co-expressed with the acb gene cluster over the course of the cultivation, including eleven transcriptional regulators (e.g. ACSP50_0424), two sigma factors (ACSP50_0644, ACSP50_6006) and further genes, which have not previously been in focus of acarbose research in Actinoplanes sp. SE50/110.Conclusion: In conclusion, we have demonstrated, that a genome wide transcriptome and proteome analysis in a high temporal resolution is well suited to study the acarbose biosynthesis and the transcriptional and post-transcriptional regulation thereof.

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MicroRNA 630 Represses NANOG Expression through Transcriptional and Post-Transcriptional Regulation in Human Embryonal Carcinoma Cells

International Journal of Molecular Sciences ◽

10.3390/ijms23010046 ◽

2021 ◽

Vol 23 (1) ◽

pp. 46

Author(s):

Wing-Keung Chu ◽

Li-Man Hung ◽

Chun-Wei Hou ◽

Jan-Kan Chen

Keyword(s):

Transcriptional Regulation ◽

Embryonal Carcinoma ◽

Carcinoma Cell ◽

Embryonic Stem ◽

Embryonal Carcinoma Cell ◽

Pluripotency Factors ◽

Nanog Expression ◽

A Genome ◽

Target Sites ◽

Post Transcriptional Regulation

The pluripotent transcription factor NANOG is essential for maintaining embryonic stem cells and driving tumorigenesis. We previously showed that PKC activity is involved in the regulation of NANOG expression. To explore the possible involvement of microRNAs in regulating the expression of key pluripotency factors, we performed a genome-wide analysis of microRNA expression in the embryonal carcinoma cell line NT2/D1 in the presence of the PKC activator, PMA. We found that MIR630 was significantly upregulated in PMA-treated cells. Experimentally, we showed that transfection of MIR630 mimic into embryonal carcinoma cell lines directly targeted the 3′UTR of OCT4, SOX2, and NANOG and markedly suppressed their expression. RNAhybrid and RNA22 algorithms were used to predict miRNA target sites in the NANOG 3’UTR, four possible target sites of MIR630 were identified. To examine the functional interaction between MIR630 and NANOG mRNA, the predicted MIR630 target sites in the NANOG 3’UTR were deleted and the activity of the reporters were compared. After targeted mutation of the predicted MIR630 target sites, the MIR630 mimic inhibited NANOG significantly less than the wild-type reporters. It is worth noting that mutation of a single putative binding site in the 3’UTR of NANOG did not completely abolish MIR630-mediated suppression, suggesting that MIR630 in the NANOG 3’UTR may have multiple binding sites and act together to maximally repress NANOG expression. Interestingly, MIR630 mimics significantly downregulated NANOG gene transcription. Exogenous expression of OCT4, SOX2, and NANOG lacking the 3’UTR almost completely rescued the reduced transcriptional activity of MIR630. MIR630 mediated the expression of differentiation markers in NT2/D1 cells, suggesting that MIR630 leads to the differentiation of NT2/D1 cell. Our findings show that MIR630 represses NANOG through transcriptional and post-transcriptional regulation, suggesting a direct link between core pluripotency factors and MIR630.

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The expression of the acarbose biosynthesis gene cluster in Actinoplanes sp. SE50/110 is dependent on the growth phase

BMC Genomics ◽

10.1186/s12864-020-07194-6 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Julian Droste ◽

Vera Ortseifen ◽

Lena Schaffert ◽

Marcus Persicke ◽

Susanne Schneiker-Bekel ◽

...

Keyword(s):

Transcriptional Regulation ◽

Stationary Phase ◽

Gene Cluster ◽

Growth Phase ◽

Formation Rate ◽

High Temporal Resolution ◽

Biosynthesis Gene Cluster ◽

Metabolic Switch ◽

A Genome ◽

Post Transcriptional Regulation

Abstract Background Actinoplanes sp. SE50/110 is the natural producer of the diabetes mellitus drug acarbose, which is highly produced during the growth phase and ceases during the stationary phase. In previous works, the growth-dependency of acarbose formation was assumed to be caused by a decreasing transcription of the acarbose biosynthesis genes during transition and stationary growth phase. Results In this study, transcriptomic data using RNA-seq and state-of-the-art proteomic data from seven time points of controlled bioreactor cultivations were used to analyze expression dynamics during growth of Actinoplanes sp. SE50/110. A hierarchical cluster analysis revealed co-regulated genes, which display similar transcription dynamics over the cultivation time. Aside from an expected metabolic switch from primary to secondary metabolism during transition phase, we observed a continuously decreasing transcript abundance of all acarbose biosynthetic genes from the early growth phase until stationary phase, with the strongest decrease for the monocistronically transcribed genes acbA, acbB, acbD and acbE. Our data confirm a similar trend for acb gene transcription and acarbose formation rate. Surprisingly, the proteome dynamics does not follow the respective transcription for all acb genes. This suggests different protein stabilities or post-transcriptional regulation of the Acb proteins, which in turn could indicate bottlenecks in the acarbose biosynthesis. Furthermore, several genes are co-expressed with the acb gene cluster over the course of the cultivation, including eleven transcriptional regulators (e.g. ACSP50_0424), two sigma factors (ACSP50_0644, ACSP50_6006) and further genes, which have not previously been in focus of acarbose research in Actinoplanes sp. SE50/110. Conclusion In conclusion, we have demonstrated, that a genome wide transcriptome and proteome analysis in a high temporal resolution is well suited to study the acarbose biosynthesis and the transcriptional and post-transcriptional regulation thereof.

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Genomic and Transcriptomic Analysis Identified Novel Putative Cassava lncRNAs Involved in Cold and Drought Stress

Genes ◽

10.3390/genes11040366 ◽

2020 ◽

Vol 11 (4) ◽

pp. 366

Author(s):

Rungaroon Suksamran ◽

Treenut Saithong ◽

Chinae Thammarongtham ◽

Saowalak Kalapanulak

Keyword(s):

Transcriptional Regulation ◽

Regulation Of Gene Expression ◽

Gene Families ◽

Cellular Processes ◽

Nuclear Factor Y ◽

Genome Wide ◽

A Genome ◽

Non Coding Rnas ◽

Post Transcriptional Regulation ◽

Genome Wide Study

Long non-coding RNAs (lncRNAs) play important roles in the regulation of complex cellular processes, including transcriptional and post-transcriptional regulation of gene expression relevant for development and stress response, among others. Compared to other important crops, there is limited knowledge of cassava lncRNAs and their roles in abiotic stress adaptation. In this study, we performed a genome-wide study of ncRNAs in cassava, integrating genomics- and transcriptomics-based approaches. In total, 56,840 putative ncRNAs were identified, and approximately half the number were verified using expression data or previously known ncRNAs. Among these were 2229 potential novel lncRNA transcripts with unmatched sequences, 250 of which were differentially expressed in cold or drought conditions, relative to controls. We showed that lncRNAs might be involved in post-transcriptional regulation of stress-induced transcription factors (TFs) such as zinc-finger, WRKY, and nuclear factor Y gene families. These findings deepened our knowledge of cassava lncRNAs and shed light on their stress-responsive roles.

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