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The effect of heterogeneous Transcription Start Sites (TSS) on the translatome: implications for the mammalian cellular phenotype

Overview of attention for article published in BMC Genomics, November 2015
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Title
The effect of heterogeneous Transcription Start Sites (TSS) on the translatome: implications for the mammalian cellular phenotype
Published in
BMC Genomics, November 2015
DOI 10.1186/s12864-015-2179-8
Pubmed ID
Authors

Francois-Xavier Dieudonné, Patrick B. F. O’Connor, Pascale Gubler-Jaquier, Haleh Yasrebi, Beatrice Conne, Sergey Nikolaev, Stylianos Antonarakis, Pavel V. Baranov, Joseph Curran

Abstract

The 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. In 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). The 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.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 3%
Sweden 1 3%
Unknown 37 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 16 41%
Researcher 9 23%
Other 3 8%
Student > Bachelor 3 8%
Student > Master 2 5%
Other 5 13%
Unknown 1 3%
Readers by discipline Count As %
Agricultural and Biological Sciences 18 46%
Biochemistry, Genetics and Molecular Biology 12 31%
Neuroscience 3 8%
Engineering 2 5%
Medicine and Dentistry 1 3%
Other 1 3%
Unknown 2 5%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 November 2015.
All research outputs
#4,599,970
of 8,582,592 outputs
Outputs from BMC Genomics
#3,811
of 6,011 outputs
Outputs of similar age
#153,309
of 299,965 outputs
Outputs of similar age from BMC Genomics
#318
of 456 outputs
Altmetric has tracked 8,582,592 research outputs across all sources so far. This one is in the 27th percentile – i.e., 27% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,011 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
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We're also able to compare this research output to 456 others from the same source and published within six weeks on either side of this one. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.