| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Ladds, MJGW, et al.
(author)
-
Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2071-
-
Journal article (peer-reviewed)abstract
- The original PDF version of this Article listed the authors as “Marcus J.G.W. Ladds,” where it should have read “Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond et al.#”.Also in the PDF version, it was incorrectly stated that “Correspondence and requests for materials should be addressed to S. Lín.”, instead of the correct “Correspondence and requests for materials should be addressed to S. Laín.”This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Li, B, et al.
(author)
-
Differential regulation of mRNA stability modulates transcriptional memory and facilitates environmental adaptation
- 2023
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 910-
-
Journal article (peer-reviewed)abstract
- Transcriptional memory, by which cells respond faster to repeated stimuli, is key for cellular adaptation and organism survival. Chromatin organization has been shown to play a role in the faster response of primed cells. However, the contribution of post-transcriptional regulation is not yet explored. Here we perform a genome-wide screen to identify novel factors modulating transcriptional memory in S. cerevisiae in response to galactose. We find that depletion of the nuclear RNA exosome increases GAL1 expression in primed cells. Our work shows that gene-specific differences in intrinsic nuclear surveillance factor association can enhance both gene induction and repression in primed cells. Finally, we show that primed cells present altered levels of RNA degradation machinery and that both nuclear and cytoplasmic mRNA decay modulate transcriptional memory. Our results demonstrate that mRNA post-transcriptional regulation, and not only transcription regulation, should be considered when investigating gene expression memory.
|
|
| 26. |
- Li, BN, et al.
(author)
-
Differential regulation of mRNA stability modulates transcriptional memory and facilitates environmental adaptation
- 2023
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 910-
-
Journal article (peer-reviewed)abstract
- Transcriptional memory, by which cells respond faster to repeated stimuli, is key for cellular adaptation and organism survival. Chromatin organization has been shown to play a role in the faster response of primed cells. However, the contribution of post-transcriptional regulation is not yet explored. Here we perform a genome-wide screen to identify novel factors modulating transcriptional memory in S. cerevisiae in response to galactose. We find that depletion of the nuclear RNA exosome increases GAL1 expression in primed cells. Our work shows that gene-specific differences in intrinsic nuclear surveillance factor association can enhance both gene induction and repression in primed cells. Finally, we show that primed cells present altered levels of RNA degradation machinery and that both nuclear and cytoplasmic mRNA decay modulate transcriptional memory. Our results demonstrate that mRNA post-transcriptional regulation, and not only transcription regulation, should be considered when investigating gene expression memory.
|
|
| 27. |
|
|
| 28. |
- Liang, S, et al.
(author)
-
Transcriptional mutagenesis dramatically alters genome-wide p53 transactivation landscape
- 2020
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 13513-
-
Journal article (peer-reviewed)abstract
- The transcriptional error rate can be significantly increased by the presence of DNA lesions that instruct mis-insertion during transcription; a process referred to as transcriptional mutagenesis (TM) that can result in altered protein function. Herein, we determined the effect of O6-methylguanine (O6-meG) on transcription and subsequent transactivation activity of p53 in human lung H1299 cells. Levels of TM and effects on transactivation were determined genome wide by RNA-seq. Results showed that 47% of all p53 transcripts contained an uridine misincorporation opposite the lesion at 6 h post transfection, which was decreased to 18% at 24 h. TM at these levels reduced DNA binding activity of p53 to 21% and 80% compared to wild type p53, respectively. Gene expression data were analysed to identify differentially expressed genes due to TM of p53. We show a temporal repression of transactivation of > 100 high confidence p53 target genes including regulators of the cell cycle, DNA damage response and apoptosis. In addition, TM repressed the transcriptional downregulation by p53 of several negative regulators of proliferation and differentiation. Our work demonstrates that TM, even when restricting its effect to an individual transcription factor, has the potential to alter gene expression programs and diversify cellular phenotypes.
|
|
| 29. |
- Nersisyan, L, et al.
(author)
-
Improved computational analysis of ribosome dynamics from 5'P degradome data using fivepseq
- 2020
-
In: NAR genomics and bioinformatics. - : Oxford University Press (OUP). - 2631-9268. ; 2:4, s. lqaa099-
-
Journal article (peer-reviewed)abstract
- In eukaryotes, 5′–3′ co-translation degradation machinery follows the last translating ribosome providing an in vivo footprint of its position. Thus, 5′ monophosphorylated (5′P) degradome sequencing, in addition to informing about RNA decay, also provides information regarding ribosome dynamics. Multiple experimental methods have been developed to investigate the mRNA degradome; however, computational tools for their reproducible analysis are lacking. Here, we present fivepseq: an easy-to-use application for analysis and interactive visualization of 5′P degradome data. This tool performs both metagene- and gene-specific analysis, and enables easy investigation of codon-specific ribosome pauses. To demonstrate its ability to provide new biological information, we investigate gene-specific ribosome pauses in Saccharomyces cerevisiae after eIF5A depletion. In addition to identifying pauses at expected codon motifs, we identify multiple genes with strain-specific degradation frameshifts. To show its wide applicability, we investigate 5′P degradome from Arabidopsis thaliana and discover both motif-specific ribosome protection associated with particular developmental stages and generally increased ribosome protection at termination level associated with age. Our work shows how the use of improved analysis tools for the study of 5′P degradome can significantly increase the biological information that can be derived from such datasets and facilitate its reproducible analysis.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Thomas, QA, et al.
(author)
-
Transcript isoform sequencing reveals widespread promoter-proximal transcriptional termination in Arabidopsis
- 2020
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 2589-
-
Journal article (peer-reviewed)abstract
- RNA polymerase II (RNAPII) transcription converts the DNA sequence of a single gene into multiple transcript isoforms that may carry alternative functions. Gene isoforms result from variable transcription start sites (TSSs) at the beginning and polyadenylation sites (PASs) at the end of transcripts. How alternative TSSs relate to variable PASs is poorly understood. Here, we identify both ends of RNA molecules in Arabidopsis thaliana by transcription isoform sequencing (TIF-seq) and report four transcript isoforms per expressed gene. While intragenic initiation represents a large source of regulated isoform diversity, we observe that ~14% of expressed genes generate relatively unstable short promoter-proximal RNAs (sppRNAs) from nascent transcript cleavage and polyadenylation shortly after initiation. The location of sppRNAs correlates with the position of promoter-proximal RNAPII stalling, indicating that large pools of promoter-stalled RNAPII may engage in transcriptional termination. We propose that promoter-proximal RNAPII stalling-linked to premature transcriptional termination may represent a checkpoint that governs plant gene expression.
|
|
| 36. |
|
|
| 37. |
- Wei, W, et al.
(author)
-
Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast
- 2019
-
In: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 29:12, s. 1974-1984
-
Journal article (peer-reviewed)abstract
- Cryptic transcription is widespread and generates a heterogeneous group of RNA molecules of unknown function. To improve our understanding of cryptic transcription, we investigated their transcription start site (TSS) usage, chromatin organization, and posttranscriptional consequences in Saccharomyces cerevisiae. We show that TSSs of chromatin-sensitive internal cryptic transcripts retain comparable features of canonical TSSs in terms of DNA sequence, directionality, and chromatin accessibility. We define the 5′ and 3′ boundaries of cryptic transcripts and show that, contrary to RNA degradation–sensitive ones, they often overlap with the end of the gene, thereby using the canonical polyadenylation site, and associate to polyribosomes. We show that chromatin-sensitive cryptic transcripts can be recognized by ribosomes and may produce truncated polypeptides from downstream, in-frame start codons. Finally, we confirm the presence of the predicted polypeptides by reanalyzing N-terminal proteomic data sets. Our work suggests that a fraction of chromatin-sensitive internal cryptic promoters initiates the transcription of alternative truncated mRNA isoforms. The expression of these chromatin-sensitive isoforms is conserved from yeast to human, expanding the functional consequences of cryptic transcription and proteome complexity.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
