GC content shapes mRNA storage and decay in human cells.

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• The interplay between messenger RNA (mRNA) translation and decay is crucial for gene expression but remains incompletely understood.
• Post-transcriptional regulation governs mRNA fate, influencing protein production and cellular function.

Purpose of the Study:

• To elucidate the rules governing the interplay between mRNA translation and decay.
• To investigate the role of GC content in mRNA localization, translation efficiency, and stability.

Main Methods:

• Integrated analysis of P-body transcriptome data with transcriptomes from silenced decay/repression factors.
• Incorporation of crosslinking, immunoprecipitation (CLIP) and related datasets.
• Comparative analysis of AU-rich versus GC-rich mRNA populations.

Main Results:

• GC content is a central determinant of mRNA fate, including P-body localization, translation efficiency, and stability.
• P-bodies preferentially contain AU-rich mRNAs, characterized by low protein yield due to codon usage.
• AU-rich and GC-rich transcripts exhibit distinct decay pathways, and targets of sequence-specific RNA-binding proteins (RBPs) and microRNAs (miRNAs) are biased by GC content.

Conclusions:

• An integrated model of post-transcriptional control in human cells is proposed, where translation regulation primarily targets inefficiently translated AU-rich mRNAs.
• Control of mRNA decay at the 5' end primarily affects optimally translated GC-rich mRNAs.
• GC content acts as a key molecular signature influencing distinct mRNA regulatory pathways.