MRNA deadenylation modeling at permissive and stress conditions reveals complex relations to decay
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PROVIDER: PRJEB75356 | ENA |
REPOSITORIES: ENA
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Project description:mRNA deadenylation modeling at permissive and stress conditions reveals complex relations to decay
| PRJNA1138735 | ENA
Project description:The prevailing model postulates that complete cytoplasmic polyadenosine tail (pA-tail) deadenylation is essential for initiating mRNA decapping and subsequent degradation. To investigate this, we conducted direct RNA sequencing of yeast mRNAs derived from steady-state and stress condition chase experiments. Subsequently, we developed a numerical model based on a modified gamma distribution function, which estimated the transcriptomic deadenylation rate at 10 A/min. A simplified independent method, based on the delineation of quantile pA-tail values, showed a correlation between the decay and deadenylation rates of individual mRNA, which appeared consistent within functional transcript groups and associated with to codon optimality. Notably, these rates varied during the stress response. Detailed analysis of ribosomal protein-coding mRNAs (RPG mRNAs), constituting 40 % of the transcriptome, singled out this transcript group. While RPG mRNA deadenylation and decay accelerated under heat stress, their degradation could proceed even when deadenylation was blocked, depending entirely on ongoing nuclear export. Our findings support the general primary function of deadenylation in dictating decapping onset, while also demonstrating complex relations between these processes.
2024-09-11 | GSE272785 | GEO
Project description:MicroRNAs regulate gene expression through deadenylation, repression and mRNA decay. However, the contribution of each mechanism in non-steady-state situations remains unclear. We monitored the impact of miR-430 on ribosome occupancy of endogenous mRNAs in wild type and dicer mutants lacking mature miR-430. Our results indicate that miR-430 reduces the number of ribosomes on target mRNAs before causing mRNA decay. Translational repression occurs before complete deadenylation, and disrupting deadenylation using an internal poly(A) tail did not block target repression. Finally, we observe that ribosome density along the length of the target mRNA remains constant, suggesting that translational repression occurs by reducing the initiation rate rather than reducing elongation or causing ribosomal drop-off. In summary, our results show that miR-430 regulates translation initiation before inducing mRNA decay. Time course parallel ribosome profiling and input mRNA quantification in wildtype and MZdicer mutant embryos
2012-03-15 | E-GEOD-34743 | biostudies-arrayexpress
Project description:Complete cytoplasmic polyadenosine tail (polyA-tail) deadenylation is thought to be essential for initiating mRNA decapping and subsequent degradation. To investigate this prevalent model, we conducted direct RNA sequencing of S. cerevisiae mRNAs derived from chase experiments under steady-state and stress condition. Subsequently, we developed a numerical model based on a modified gamma distribution function, which estimated the transcriptomic deadenylation rate at 10 A/min. A simplified independent method, based on the delineation of quantile polyA-tail values, showed a correlation between the decay and deadenylation rates of individual mRNAs, which appeared consistent within functional transcript groups and associated with codon optimality. Notably, these rates varied during the stress response. Detailed analysis of ribosomal protein-coding mRNAs (RPG mRNAs), constituting 40 % of the transcriptome, singled out this transcript group. While deadenylation and decay of RPG mRNAs accelerated under heat stress, their degradation could proceed even when deadenylation was blocked, depending entirely on ongoing nuclear export. Our findings support the general primary function of deadenylation in dictating the onset of decapping, while also demonstrating complex relations between these processes.
| S-SCDT-10_1038-S44318-024-00258-3 | biostudies-other
Project description:Poly(A) tails protect RNAs from degradation and deadenylation rates determine RNA stability. Deadenylation has mostly been investigated within the cytoplasm and the dynamics of poly(A) tail length after transcription are not well understood. Combining long-read sequencing with metabolic labeling and cell fractionations, we investigate deadenylation dynamics of newly synthesized poly(A) tails in vitro and in vivo. We report evidence for genome-wide synthesis of poly(A) tails longer than 200 nt which are enriched upon splicing inhibition. Metabolic labeling reveals rapid deadenylation of poly(A) tails within minutes after transcription. Fractionation experiments show that initial deadenylation is a nuclear process, and that different classes of transcripts, including long noncoding RNAs, have distinctive nuclear poly(A) tail lengths. Modelling deadenylation dynamics predicts that deadenylation in the nucleus is by an order of magnitude faster than in the cytoplasm. In summary, we suggest nuclear deadenylation as a novel regulatory layer which may determine stability and abundance before mRNAs reach the cytoplasm.
2023-01-07 | GSE188539 | GEO
Project description:MicroRNAs regulate gene expression through deadenylation, repression and mRNA decay. However, the contribution of each mechanism in non-steady-state situations remains unclear. We monitored the impact of miR-430 on ribosome occupancy of endogenous mRNAs in wild type and dicer mutants lacking mature miR-430. Our results indicate that miR-430 reduces the number of ribosomes on target mRNAs before causing mRNA decay. Translational repression occurs before complete deadenylation, and disrupting deadenylation using an internal poly(A) tail did not block target repression. Finally, we observe that ribosome density along the length of the target mRNA remains constant, suggesting that translational repression occurs by reducing the initiation rate rather than reducing elongation or causing ribosomal drop-off. In summary, our results show that miR-430 regulates translation initiation before inducing mRNA decay.
2012-03-15 | GSE34743 | GEO
Project description:The oocyte-to-embryo transition (OET) occurs in the absence of new transcription and relies on post-transcriptional gene regulation, including translational control by mRNA poly(A) tail regulation, where cytoplasmic polyadenylation activates translation and deadenylation leads to translational repression and decay. However, how the transcriptome-wide landscape of mRNA poly(A) tails shapes translation across the OET in mammals remains unknown. Here, we performed long-read RNA sequencing to uncover poly(A) tail lengths and mRNA abundance transcriptome-wide in mice across five stages of development from oocyte to embryo. Integrating these data with recently published ribosome profiling data, we demonstrate that poly(A) tail length is coupled to translational efficiency across the entire OET. We uncover an extended wave of global deadenylation during fertilization, which sets up a switch in translation control between the oocyte and embryo. In the oocyte, short-tailed maternal mRNAs that resist deadenylation in the oocyte are translationally activated, whereas large groups of mRNAs deadenylated without decay in the oocyte are later readenylated to drive translation activation in the early embryo. Our findings provide an important resource and insight into the mechanisms by which cytoplasmic polyadenylation and deadenylation dynamically shape poly(A) tail length in a stage-specific manner to orchestrate development from oocyte to embryo in mammals.
2024-03-14 | GSE228001 | GEO
Project description:Nonsense-mediated mRNA decay (NMD) controls gene expression by eliminating mRNAs with premature or aberrant translation termination. Degradation of NMD substrates is initiated by the central NMD factor UPF1, which recruits the endonuclease SMG6 and the deadenylation-promoting SMG5/7 complex. Here we map transcriptome-wide sites of SMG6-mediated endocleavage via 3′ fragment capture and degradome sequencing.
2017-06-01 | E-MTAB-3625 | biostudies-arrayexpress
Project description:RNA tails play integral roles in the control of mRNA translation and decay. Guanylation of poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TUT3 (PAPD5) and TUT5 (PAPD7) (TUT3/5) as the enzymes responsible for mRNA guanylation. Purified TUT3/5 predominantly incorporate GTPs to generate a mixed poly(A) tail with intermittent non-adenosine residues. A single guanosine is sufficient to impede the deadenylation complex (CCR4-NOT) which trims the tail and exposes guanosine at the 3′ end. Consistently, the depletion of TUT3/5 leads to a decrease in mRNA half-life and abundance in cells. Thus, TUT3/5 produce a mixed tail which shields the mRNA from rapid deadenylation. Our study unveils the role of mixed tailing, and expands the complexity of post-transcriptional gene regulation.
2019-06-09 | GSE116349 | GEO
Project description:RNA tails play integral roles in the control of mRNA translation and decay. Guanylation of poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TUT3 (PAPD5) and TUT5 (PAPD7) (TUT3/5) as the enzymes responsible for mRNA guanylation. Purified TUT3/5 predominantly incorporate GTPs to generate a mixed poly(A) tail with intermittent non-adenosine residues. A single guanosine is sufficient to impede the deadenylation complex (CCR4-NOT) which trims the tail and exposes guanosine at the 3′ end. Consistently, the depletion of TUT3/5 leads to a decrease in mRNA half-life and abundance in cells. Thus, TUT3/5 produce a mixed tail which shields the mRNA from rapid deadenylation. Our study unveils the role of mixed tailing, and expands the complexity of post-transcriptional gene regulation.
2019-06-09 | GSE115529 | GEO