Translatomics: The Global View of Translation

Abstract

In all kingdoms of life, proteins are synthesized by ribosomes in a process referred to as translation. The amplitude of translational regulation exceeds the sum of transcription, mRNA degradation and protein degradation. Therefore, it is essential to investigate translation in a global scale. Like the other "omics"-methods, translatomics investigates the totality of the components in the translation process, including but not limited to translating mRNAs, ribosomes, tRNAs, regulatory RNAs and nascent polypeptide chains. Technical advances in recent years have brought breakthroughs in the investigation of these components at global scale, both for their composition and dynamics. These methods have been applied in a rapidly increasing number of studies to reveal multifaceted aspects of translation control. The process of translation is not restricted to the conversion of mRNA coding sequences into polypeptide chains, it also controls the composition of the proteome in a delicate and responsive way. Therefore, translatomics has extended its unique and innovative power to many fields including proteomics, cancer research, bacterial stress response, biological rhythmicity and plant biology. Rational design in translation can enhance recombinant protein production for thousands of times. This brief review summarizes the main state-of-the-art methods of translatomics, highlights recent discoveries made in this field and introduces applications of translatomics on basic biological and biomedical research.

Keywords: RNC-mRNA; RNC-seq; Ribo-seq; polysome profiling; translation regulation; translatomics.

Figure 1

The major translatomic methods which investigate translating RNAs.

Figure 2

The major methods to investigate nascent peptides. (A) Translational pausing sites and the co-translational folding of nascent peptides. Proteinase K limited digestioni is often used to detect the folding state of nascent peptides. (B) High-throughput methods to identify and quantify nascent peptides.

Figure 3

Two-dimensional control mode of translation initiation efficiency (TR) and translation elongation rate (EVI) Most genes are of Balanced mode, with moderate TR and moderate EVI. A small fraction of genes undergoes active translational initiation and rapid elongation and thus are very efficiently produced. These genes under “Productivity mode” do not require co-translational folding for its final conformation; thus, rapid elongation do not impair their functions. Another small fraction of genes is synthesized with moderate TR but low EVI, indicating that there are considerable translational pausing sites along their mRNAs for better co-translational folding quality to ensure their functionality and thus are of “Quality mode.” Simultaneous high TR and low EVI would result in ribosome jamming and thus were eliminated during the evolution.