ArticleBMC genomics2015
The effect of heterogeneous Transcription Start Sites (TSS) on the translatome: implications for the mammalian cellular phenotype.
Article in BMC genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- The regulatory landscape of 5' UTRs in translational control during zebrafish embryogenesis.Developmental cell · 2025Article
- mRNA Transcript Variants Expressed in Mammalian Cells.International journal of molecular sciences · 2025Review
- The regulatory landscape of 5' UTRs in translational control during zebrafish embryogenesis.bioRxiv : the preprint server for biology · 2023Article
- CamoTSS: analysis of alternative transcription start sites for cellular phenotypes and regulatory patterns from 5' scRNA-seq data.Nature communications · 2023Article
- The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs.PLoS biology · 2023Article
- Selective Concurrence of the Long Non-Coding RNA MALAT1 and the Polycomb Repressive Complex 2 to Promoter Regions of Active Genes in MCF7 Breast Cancer Cells.Current issues in molecular biology · 2023Article
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- TIA1 Loss Exacerbates Fatty Liver Disease but Exerts a Dual Role in Hepatocarcinogenesis.Cancers · 2022Article
- Global approaches for profiling transcription initiation.Cell reports methods · 2021Review
- eIF4E3 forms an active eIF4F complex during stresses (eIF4FS) targeting mTOR and re-programs the translatome.Nucleic acids research · 2021Article
- Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development.PLoS genetics · 2020Article
- Translational Control in Cancer.Cold Spring Harbor perspectives in biology · 2019Review
- Evidence for an Integrated Gene Repression Mechanism Based on mRNA Isoform Toggling in Human Cells.G3 (Bethesda, Md.) · 2019Article
- The Untranslated Regions of mRNAs in Cancer.Trends in cancer · 2019Review
- Optimization of carbon and energy utilization through differential translational efficiency.Nature communications · 2018Article
- Bcr-Abl regulation of sphingomyelin synthase 1 reveals a novel oncogenic-driven mechanism of protein up-regulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Application of aRNA (New York, N.Y.) · 2018Article
- Decoding sORF translation - from small proteins to gene regulation.RNA biology · 2016Review
- What Is the Impact of mRNA 5' TL Heterogeneity on Translational Start Site Selection and the Mammalian Cellular Phenotype?Frontiers in genetics · 2016Review
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9 authors.
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Abstract
backgroundThe genetic program, as manifested as the cellular phenotype, is in large part dictated by the cell's protein composition. Since characterisation of the proteome remains technically laborious it is attractive to define the genetic expression profile using the transcriptome. However, the transcriptional landscape is complex and it is unclear as to what extent it reflects the ribosome associated mRNA population (the translatome). This is particularly pertinent for genes using multiple transcriptional start sites (TSS) generating mRNAs with heterogeneous 5' transcript leaders (5'TL). Furthermore, the relative abundance of the TSS gene variants is frequently cell-type specific. Indeed, promoter switches have been reported in pathologies such as cancer. The consequences of this 5'TL heterogeneity within the transcriptome for the translatome remain unresolved. This is not a moot point because the 5'TL plays a key role in regulating mRNA recruitment onto polysomes.
resultsIn this article, we have characterised both the transcriptome and translatome of the MCF7 (tumoural) and MCF10A (non-tumoural) cell lines. We identified ~550 genes exhibiting differential translation efficiency (TE). In itself, this is maybe not surprising. However, by focusing on genes exhibiting TSS heterogeneity we observed distinct differential promoter usage patterns in both the transcriptome and translatome. Only a minor fraction of these genes belonged to those exhibiting differential TE. Nonetheless, reporter assays demonstrated that the TSS variants impacted on the translational readout both quantitatively (the overall amount of protein expressed) and qualitatively (the nature of the proteins expressed).
conclusionsThe results point to considerable and distinct cell-specific 5'TL heterogeneity within both the transcriptome and translatome of the two cell lines analysed. This observation is in-line with the ribosome filter hypothesis which posits that the ribosomal machine can selectively filter information from within the transcriptome. As such it cautions against the simple extrapolation transcriptome → proteome. Furthermore, polysomal occupancy of specific gene 5'TL variants may also serve as novel disease biomarkers.
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