Rapid nuclear deadenylation of mammalian messenger RNA
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE188539 | GEO | 2023/01/07
REPOSITORIES: GEO
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Project description:Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other 'housekeeping' proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA mediated deadenylation concurrently shifts from translational repression to mRNA destabilization. 64 samples from a variety of species
2014-01-29 | E-GEOD-52809 | biostudies-arrayexpress
Project description:Nascent mRNA is endowed with a poly(A) tail, which is subject to gradual deadenylation in the cytoplasm, followed by mRNA degradation. Deadenylation and degradation rates are typically correlated, rendering it difficult to dissect the individual determinants governing each of these processes. In addition, the mechanistic basis for the coupling between deadenylation and degradation and the extent to which the two can be decoupled are largely unknown. Here we developed an approach allowing systematic, robust and multiplexed quantification of poly(A) tails. Our results suggest that in yeast, exclusively during meiosis, mRNA deadenylation and degradation rates are decoupled. The decoupled regime in meiosis allowed us to discover transcript length as a major determinant of deadenylation rates and as a key contributor to the reshaping of poly(A) tail lengths in meiosis. The meiosis-specific decoupling also led to unique positive associations between poly(A) tail length and gene expression. The decoupling of degradation from deadenylation is also strongly associated with a focal localization pattern of the RNA degradation factor Xrn1 and can be phenocopied by deletion of Xrn1 under non-meiotic conditions. Importantly, the association of transcript length with deadenylation rates is conserved across eukaryotes. This study uncovers a new factor that shapes deadenylation rate and discovers a unique context in which degradation is decoupled from deadenylation.
2021-10-10 | GSE171329 | GEO
Project description:Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other 'housekeeping' proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA mediated deadenylation concurrently shifts from translational repression to mRNA destabilization.
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Project description:Poly(A) tails are critical for mRNA stability and translation. However, recent studies have challenged this view, showing that poly(A) tail length and translation efficiency are decoupled in non-embryonic cells. Using TAIL-seq and ribosome profiling, we investigate poly(A) tail dynamics and translational control in the somatic cell cycle. We find dramatic changes in poly(A) tail lengths of cell cycle regulatory genes like CDK1, TOP2A, and FBXO5, explaining their translational repression in M phase. We also find that poly(A) tail length is coupled to translation when the poly(A) tail is <20 nucleotides. However, as most genes have >20 nucleotide poly(A) tails, their translation is regulated mainly via poly(A) tail length-independent mechanisms during the cell cycle. Specifically, we find that terminal oligopyrimidine (TOP) tract-containing transcripts escape global translational suppression in M phase and are actively translated. Our quantitative and comprehensive data provide a revised view of translational control in the somatic cell cycle. HeLa cells were synchronized at S or M phase, and subject to RNA-seq, ribosome profiling and TAIL-seq analysis.
2016-04-04 | E-GEOD-79664 | biostudies-arrayexpress
Project description:The poly(A) tail appended to the 3’ end of many eukaryotic transcripts plays a key role in the stability, nuclear transport, and translation of the RNA. These roles are largely mediated by the Poly(A) Binding Proteins (PABPs) that coat the poly(A) tails and interact with various proteins involved in the biogenesis and function of the RNA. While it is well established that the nuclear PABP (PABPN) binds newly synthesized poly(A) tails and is apparently replaced by the cytoplasmic PABP (PABPC) on transcripts exported to the cytoplasm, the distribution of transcripts for different genes or isoforms of the same gene on these distinct PABPs has not been investigated on a genome-wide scale. Here, we analyzed the identity, splicing status, poly(A) tail size, and translation status of RNAs co-immunoprecipitated with endogenous PABPN or PABPC in human cells. At steady state, many protein coding and non-coding RNAs exhibit strong bias for association with PABPN or PABPC. While PABPN-enriched transcripts more often were incompletely spliced and harbored longer poly(A) tails and PABPC-enriched RNAs tended to have longer half-lives and higher translation efficiency, there are curious outliers. Overall, our study reveals the landscape of RNAs bound by PABPN and PABPC, providing new details that support and advance the current understanding of the roles these proteins play in poly(A) tail synthesis, maintenance and function.
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Project description:The poly(A) tail appended to the 3’ end of many eukaryotic transcripts plays a key role in the stability, nuclear transport, and translation of the RNA. These roles are largely mediated by the Poly(A) Binding Proteins (PABPs) that coat the poly(A) tails and interact with various proteins involved in the biogenesis and function of the RNA. While it is well established that the nuclear PABP (PABPN) binds newly synthesized poly(A) tails and is apparently replaced by the cytoplasmic PABP (PABPC) on transcripts exported to the cytoplasm, the distribution of transcripts for different genes or isoforms of the same gene on these distinct PABPs has not been investigated on a genome-wide scale. Here, we analyzed the identity, splicing status, poly(A) tail size, and translation status of RNAs co-immunoprecipitated with endogenous PABPN or PABPC in human cells. At steady state, many protein coding and non-coding RNAs exhibit strong bias for association with PABPN or PABPC. While PABPN-enriched transcripts more often were incompletely spliced and harbored longer poly(A) tails and PABPC-enriched RNAs tended to have longer half-lives and higher translation efficiency, there are curious outliers. Overall, our study reveals the landscape of RNAs bound by PABPN and PABPC, providing new details that support and advance the current understanding of the roles these proteins play in poly(A) tail synthesis, maintenance and function.
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Project description:The poly(A) tail appended to the 3’ end of many eukaryotic transcripts plays a key role in the stability, nuclear transport, and translation of the RNA. These roles are largely mediated by the Poly(A) Binding Proteins (PABPs) that coat the poly(A) tails and interact with various proteins involved in the biogenesis and function of the RNA. While it is well established that the nuclear PABP (PABPN) binds newly synthesized poly(A) tails and is apparently replaced by the cytoplasmic PABP (PABPC) on transcripts exported to the cytoplasm, the distribution of transcripts for different genes or isoforms of the same gene on these distinct PABPs has not been investigated on a genome-wide scale. Here, we analyzed the identity, splicing status, poly(A) tail size, and translation status of RNAs co-immunoprecipitated with endogenous PABPN or PABPC in human cells. At steady state, many protein coding and non-coding RNAs exhibit strong bias for association with PABPN or PABPC. While PABPN-enriched transcripts more often were incompletely spliced and harbored longer poly(A) tails and PABPC-enriched RNAs tended to have longer half-lives and higher translation efficiency, there are curious outliers. Overall, our study reveals the landscape of RNAs bound by PABPN and PABPC, providing new details that support and advance the current understanding of the roles these proteins play in poly(A) tail synthesis, maintenance and function.
2022-03-30 | GSE195493 | GEO
Project description:Poly(A) tails are critical for mRNA stability and translation. However, recent studies have challenged this view, showing that poly(A) tail length and translation efficiency are decoupled in non-embryonic cells. Using TAIL-seq and ribosome profiling, we investigate poly(A) tail dynamics and translational control in the somatic cell cycle. We find dramatic changes in poly(A) tail lengths of cell cycle regulatory genes like CDK1, TOP2A, and FBXO5, explaining their translational repression in M phase. We also find that poly(A) tail length is coupled to translation when the poly(A) tail is <20 nucleotides. However, as most genes have >20 nucleotide poly(A) tails, their translation is regulated mainly via poly(A) tail length-independent mechanisms during the cell cycle. Specifically, we find that terminal oligopyrimidine (TOP) tract-containing transcripts escape global translational suppression in M phase and are actively translated. Our quantitative and comprehensive data provide a revised view of translational control in the somatic cell cycle.
2016-04-04 | GSE79664 | GEO
Project description:For all but a few mRNAs, the dynamics of metabolism are unknown. Here, we developed an experimental and analytical framework for examining these dynamics for mRNAs from thousands of genes. mRNAs of mouse fibroblasts exit the nucleus with diverse intragenic and intergenic poly(A)-tail lengths. Once in the cytoplasm, they have a broad (1000-fold) range of deadenylation rates, which correspond to cytoplasmic lifetimes. Indeed, degradation appears to occur primarily through deadenylation-linked mechanisms, with little contribution from endonucleolytic cleavage or deadenylation-independent decapping. Most mRNA molecules degrade only after their tail lengths fall below 25 nt. Decay rates of short-tailed mRNAs vary broadly (1000-fold) and are more rapid for short-tailed mRNAs that had previously undergone more rapid deadenylation. This coupling helps clear rapidly deadenylated mRNAs, enabling the large range in deadenylation rates to impart a similarly large range in stabilities.
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Project description:Poly(A) tails are important elements in mRNA translation and stability. However, recent genome-wide studies concluded that poly(A) tail length was generally not associated with translational efficiency in non-embryonic cells. To investigate if poly(A) tail size might be coupled to gene expression in an intact organism, we used an adapted TAIL-seq protocol to measure poly(A) tails in Caenorhabditis elegans. Surprisingly, we found that well-expressed transcripts contain relatively short, well-defined tails. This attribute appears dependent on translational efficiency, as transcripts enriched for optimal codons and ribosome association had the shortest tail sizes, while non-coding RNAs retained long tails.
2017-10-19 | GSE104501 | GEO