scholarly journals Targeted proteomics analysis revealed the imbalanced allele‐specific protein expression of carboxylesterase1 in human livers

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
Lucy Her ◽  
Jian Shi ◽  
Xinwen Wang ◽  
Hao-Jie Zhu
2018 ◽  
Author(s):  
Jian Shi ◽  
Xinwen Wang ◽  
Huaijun Zhu ◽  
Hui Jiang ◽  
Danxin Wang ◽  
...  

AbstractMeasuring allele-specific expression (ASE) is a powerful approach for identifying cis-regulatory genetic variants. Here we developed a novel targeted proteomics method for quantification of allele-specific protein expression (ASPE) based on scheduled high resolution multiple reaction monitoring (sMRM-HR) with a heavy stable isotope-labeled quantitative concatamer (QconCAT) internal protein standard. This strategy was applied to the determination of the ASPE of UGT2B15 in human livers using the common UGT2B15 nonsynonymous variant rs1902023 (i.e. Y85D) as the marker to differentiate expressions from the two alleles. The QconCAT standard contains both the wild type tryptic peptide and the Y85D mutant peptide at a ratio of 1:1 to ensure accurate measurement of the ASPE of UGT2B15. The results from 18 UGT2B15 Y85D heterozygotes revealed that the ratios between wild type Y allele and mutant D allele varied from 0.60 to 1.46, indicating the presence of cis-regulatory variants. In addition, we observed no significant correlations between the ASPE and mRNA ASE of UGT2B15, suggesting the involvement of different cis-acting variants in regulating the transcription and translation processes of the gene. This novel ASPE approach provides a powerful tool for capturing cis-genetic variants involved in post-transcription processes, an important yet understudied area of research.


2018 ◽  
Vol 17 (10) ◽  
pp. 3606-3612 ◽  
Author(s):  
Jian Shi ◽  
Xinwen Wang ◽  
Huaijun Zhu ◽  
Hui Jiang ◽  
Danxin Wang ◽  
...  

2019 ◽  
Vol 18 (3) ◽  
pp. 1458-1459
Author(s):  
Jian Shi ◽  
Xinwen Wang ◽  
Huaijun Zhu ◽  
Hui Jiang ◽  
Danxin Wang ◽  
...  

2012 ◽  
Vol 8 (1) ◽  
pp. 602 ◽  
Author(s):  
Zia Khan ◽  
Joshua S Bloom ◽  
Sasan Amini ◽  
Mona Singh ◽  
David H Perlman ◽  
...  

2018 ◽  
Vol 23 (6) ◽  
pp. 1070-1078 ◽  
Author(s):  
Hikono Aiki ◽  
Takuro Wada ◽  
Kousuke Iba ◽  
Gosuke Oki ◽  
Hitoshi Sohma ◽  
...  

2008 ◽  
Vol 13 (8b) ◽  
pp. 1809-1822 ◽  
Author(s):  
Marzia Perluigi ◽  
Alessandra Giorgi ◽  
Carla Blarzino ◽  
Federico De Marco ◽  
Cesira Foppoli ◽  
...  

2018 ◽  
Author(s):  
Chiu-An Lo ◽  
Brian E. Chen

AbstractAllelic expression from each parent-of-origin is important as a backup and to ensure that enough protein products of a gene are produced. Thus far, it is not known how each cell throughout a tissue differs in parental allele expression at the level of protein synthesis. Here, we measure the expression of the Ribosomal protein L13a (Rpl13a) from both parental alleles simultaneously in single cells in the living animal. We use genome-edited Drosophila that have a quantitative reporter of protein synthesis inserted into the endogenous Rpl13a locus. We find that individual cells can have large (>10-fold) differences in protein expression between the two parental alleles. Cells can produce protein from only one allele oftentimes, and time-lapse imaging of protein production from each parental allele in each cell showed that the imbalance in expression from one parental allele over the other can invert over time.One sentence summaryParental allele-specific protein expression varies widely across cells and over time.HighlightsWe used genome editing to insert a quantifiable protein translation reporter into the endogenous Ribosomal protein L13a gene and thus track the protein expression of both parental alleles simultaneously in every single cell in the awake animal.Cells can have a large difference in protein expression for one parental allele over the other, and this can invert over time, and can occur in clusters of cells within a tissue.We demonstrate the highly variable nature of heterozygous and homozygous definitions across single cells, and over time.Our study demonstrates a new paradigm that can be used to examine inherited epigenetic control of expression from a specific parent-of-origin allele across single clonal cells from a common progenitor in vivo.


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