Abstract
A major determinant in the efficiency of ribosome loading onto mRNAs is the 5′ TL (transcript leader or 5′ UTR). In addition, elements within this region also impact on start site selection demonstrating that it can modulate the protein readout at both quantitative and qualitative levels. With the increasing wealth of data generated by the mining of the mammalian transcriptome, it has become evident that a genes 5′ TL is not homogeneous but actually exhibits significant heterogeneity. This arises due to the utilization of alternative promoters, and is further compounded by significant variability with regards to the precise transcriptional start sites of each (not to mention alternative splicing). Consequently, the transcript for a protein coding gene is not a unique mRNA, but in-fact a complexed quasi-species of variants whose composition may respond to the changing physiological environment of the cell. Here we examine the potential impact of these events with regards to the protein readout.
Highlights
The cellular phenotype is determined mainly by the cells protein composition
The translational program can be modified rapidly, proceeding and, frequently orchestrating the later transcriptional response. It is limited by the complexity of the existing transcriptome since it is from this pool that the mRNA will be recruited to seed the polysome
With regards to the mRNA 5 Heterogeneity Protein Readout mRNA transcript, this includes alternative splicing, multiple transcriptional start sites (TSS) and termination sites (TTS) all of which can be regulated in a cell-specific manner, and all serve to couple nuclear events to the protein readout in the cytoplasm (Davuluri et al, 2008; Pal et al, 2011)
Summary
Site Selection and the Mammalian Cellular Phenotype? Front. Genet. 7:156. Elements within this region impact on start site selection demonstrating that it can modulate the protein readout at both quantitative and qualitative levels. With the increasing wealth of data generated by the mining of the mammalian transcriptome, it has become evident that a genes 5 TL is not homogeneous but exhibits significant heterogeneity. This arises due to the utilization of alternative promoters, and is further compounded by significant variability with regards to the precise transcriptional start sites of each (not to mention alternative splicing).
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