Spatiotemporal analysis of mRNA-protein relationships enhances transcriptome-based developmental inference

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• Accurate measurement of gene expression is crucial for understanding developmental processes.
• Single-cell analysis provides high spatiotemporal resolution for studying gene regulation.
• The relationship between mRNA and protein expression is complex and dynamic.

Purpose of the Study:

• To analyze mRNA and protein expression of transcription factors during C. elegans embryogenesis at single-cell resolution.
• To investigate the impact of delayed protein synthesis and protein persistence on mRNA-protein concordance.
• To develop and validate a method for inferring protein presence from mRNA expression for improved developmental analyses.

Main Methods:

• Single-cell RNA sequencing and protein quantification.
• Computational analysis of mRNA and protein expression dynamics.
• Inference of protein presence based on learned mRNA-protein relationships.

Main Results:

• Initial low co-expression of mRNA and protein increases to 73% when considering synthesis and persistence.
• Delayed protein synthesis and long-term persistence significantly influence mRNA-protein concordance.
• The developed method successfully identified tissue-specific genes and elucidated gene-cell relationships, including the role of sptf-1/SP7 in neuronal development.

Conclusions:

• Gene expression dynamics during embryogenesis are significantly influenced by protein synthesis and degradation kinetics.
• Inferring protein presence from mRNA expression enhances the accuracy of transcriptome-based developmental studies.
• This approach offers a powerful tool for unraveling gene regulatory networks and developmental mechanisms.