Parental allele-specific protein expression in single cells In vivo

Area of Science:

• Molecular Biology
• Genetics
• Developmental Biology

Background:

• Parental allele expression is crucial for sufficient protein production and acts as a backup mechanism.
• Understanding cell-to-cell variation in parental allele expression at the protein synthesis level within tissues is currently limited.

Purpose of the Study:

• To quantitatively measure simultaneous protein synthesis from both parental alleles of the Ribosomal protein L13a (Rpl13a) gene in single cells within a living animal.
• To investigate the dynamics and variability of allelic protein expression within a tissue.

Main Methods:

• Utilized genome-edited Drosophila with a quantitative reporter for protein synthesis integrated into the endogenous Rpl13a locus.
• Employed time-lapse imaging to observe protein production from each parental allele in individual cells over time.

Main Results:

• Observed substantial cell-specific differences, exceeding 10-fold, in protein expression between parental alleles.
• Found that cells frequently produce protein from only one parental allele.
• Demonstrated that the imbalance in allelic protein expression can dynamically invert over time within single cells.
• Identified the histone methyltransferase EHMT as a factor influencing these protein synthesis dynamics.

Conclusions:

• Significant variability exists in single-cell allelic protein expression, challenging the assumption of uniform expression.
• The dynamic nature of allelic imbalance suggests complex regulatory mechanisms controlling gene output at the protein level.
• EHMT plays a role in regulating the dynamics of protein synthesis from parental alleles within cells.