Post-transcriptional regulation across human tissues

Area of Science:

• Molecular Biology
• Genomics
• Proteomics

Background:

• Transcriptional and post-transcriptional regulation are key to shaping tissue-specific proteomes.
• The relative contributions of these regulatory layers to protein abundance variability remain debated.
• Existing estimates often conflate variability within and across tissues.

Purpose of the Study:

• To quantify the contribution of transcript levels to protein abundance variability within and across human tissues.
• To differentiate between mean-level variability and across-tissues variability in proteome regulation.
• To investigate the role of post-transcriptional regulation in shaping tissue-specific proteomes.

Main Methods:

• Analysis of transcript and protein abundance data across human tissues.
• Statistical modeling to separate orthogonal sources of variability (mean-level vs. across-tissues).
• Assessment of protein-to-mRNA ratios to infer post-transcriptional regulation.

Main Results:

• Scaled messenger RNA (mRNA) levels largely explain protein abundance variability within tissues (mean-level variability).
• mRNA levels do not consistently explain protein abundance differences across tissues (across-tissues variability).
• Protein-to-mRNA ratios show significant, reproducible across-tissues variability, indicating substantial post-transcriptional regulation.

Conclusions:

• Caution is advised when inferring protein fold-changes from mRNA fold-changes between different cell types.
• Post-transcriptional regulation plays a critical role in establishing tissue-type-specific proteomes.
• Measurement noise limits the accurate quantification of across-tissues variability using current methods.