Translational buffering tunes gene expression in mouse and human.

Area of Science:

• Molecular Biology
• Genomics
• Gene Regulation

Background:

• Translational buffering regulates ribosome occupancy to counteract transcriptional variations.
• Previous studies focused on yeast, leaving the conservation in mammals unclear.

Purpose of the Study:

• To investigate the prevalence and characteristics of translational buffering in human and mouse genes across various cell types.
• To determine if translational buffering is a conserved genetic property and understand its underlying mechanisms and functional implications.

Main Methods:

• Uniform analysis of 1515 matched ribosome profiling and RNA-seq datasets from human and mouse.
• Comparative analysis of ribosome occupancy and RNA level variations.
• Examination of mRNA abundance and translation efficiency relationships.
• Modeling to assess sequence features and cellular context in predicting buffering.

Main Results:

• Translational buffering is a conserved property in homologous human and mouse genes.
• Buffered genes exhibit lower protein abundance variation and are often haploinsufficient or triplosensitive.
• Sequence features alone are insufficient to predict buffering; cellular context is crucial.
• Evidence supports two distinct models of translational buffering: differential accessibility and altered translation initiation.

Conclusions:

• Translational buffering is a widespread and conserved phenomenon in mammals, crucial for precise protein dosage.
• The study expands the catalog of buffered genes and provides insights into their functional significance and regulatory mechanisms.