Death of a dogma: eukaryotic mRNAs can code for more than one protein

Area of Science:

• Molecular Biology
• Genomics
• Proteomics

Background:

• Eukaryotic messenger RNAs (mRNAs) traditionally are viewed as containing a single protein-coding open reading frame (ORF) or coding sequence (CDS).
• This single CDS concept led to the assumption that each gene produces only one protein.
• Recent evidence suggests this view is incomplete, with alternative ORFs being translated from mRNAs.

Purpose of the Study:

• To review experimental evidence for the translation of alternative ORFs from eukaryotic mRNAs.
• To challenge the dogma of a single translated CDS per mRNA.
• To explore the implications of alternative protein production for co-expression and functional interactions.

Main Methods:

• Review of existing literature and experimental data.
• Analysis of mass spectrometry (MS)-based proteomics data.
• Examination of ribosome profiling data.

Main Results:

• Experimental evidence confirms the productive translation of alternative ORFs in eukaryotic mRNAs.
• Alternative and annotated proteins are sometimes found to interact, suggesting functional links.
• Cellular machinery possesses mechanisms to translate multiple CDSs from a single mRNA.

Conclusions:

• The protein-coding potential of eukaryotic mRNAs is greater than previously assumed.
• The translation of alternative ORFs provides a mechanism for co-expressing functionally interacting proteins.
• The single translated CDS dogma in eukaryotic gene expression needs re-evaluation.