September 29th, 2024

Recent Publications Harnessing the Power of Translatomics

Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.

In this week’s Sunday papers, Sejour et al suggested that the slowly decoded rare codons were evolutionary leftovers that have no role in translation efficiency. Francisco-Velilla et al unveiled the ability of RNA-binding protein Gemin5 to form oligomers is the key to its interactions with the translation machinery. Jiang et al revealed soil conditioners can enhance grape quality by altering root gene expression to improve anthocyanin synthesis.

Enrichment of rare codons at 5' ends of genes is a spandrel caused by evolutionary sequence turnover and does not improve translation

eLife, 2024

Sejour, R., Leatherwood, J., Yurovsky, A. and Futcher, B.

Rare codon enrichment at the 5′ ends of yeast and other eukaryotic genes was for a long time thought to enhance translational efficiency by preventing ribosome collisions – the so-called ‘ramp theory’. Here the authors of this study suggest that  rare codons at 5’ positions do not facilitate translation but rather are a byproduct of rapid sequence turnover at gene termini, termed a “spandrel.”

The study reaffirms the enrichment of rare, slowly translated codons in the initial segments of yeast genes, aligning with previous observations. However, the authors. argue that this pattern is not an adaptive mechanism for translation efficiency but results from the unstable and faster turnover of these gene regions. They propose that new gene termini formed de novo often incorporate what are initially rare codons, simply because there hasn’t been sufficient evolutionary time for selection to act against them.

Analysis of ribosome density globally using ribosome profiling data suggests that mRNAs with the highest ribosome densities also have the highest conservation scores and vice versa. Furthermore, using reporter assays they show that replacing slow codons with faster, synonymous alternatives at the 5′ ends enhances gene expression, contrary to the expectation that slow translation is beneficial. Moreover, these changes did not prevent ribosomal collisions downstream, challenging the idea that slow starting ramps in translation serve a protective role.

Further analysis of ribosome profiling data shows that slowly translated regions at gene starts correlate with poorer gene expression overall, reinforcing the notion that the presence of these rare codons is a non-adaptive feature resulting from gene sequence instability.

In summary, this study challenges the traditional view of the “translational ramp” as an adaptive feature, suggesting instead that it is an evolutionary artifact with no beneficial impact on translation. This insight adds a significant layer to our understanding of gene expression regulation, highlighting the complexities of evolutionary influences on molecular biology.

Oligomerization regulates the interaction of Gemin5 with members of the SMN complex and the translation machinery

Nature Cell Death Discovery, 2024

Francisco-Velilla, R., Abellan, S., Embarc-Buh, A. and Martinez-Salas, E.

This study focuses on the structural and functional intricacies of Gemin5, a multifunctional RNA-binding protein (RBP), emphasizing its role in translational regulation. Gemin5 is part of the survival of motor neurons (SMN) complex and interacts with various cellular machinery through its distinct structural domains.

Francisco-Velilla et al reveal that Gemin5 oligomerization, particularly mediated by its tetratricopeptide repeat (TPR) domain, is crucial for its function. This oligomerization is required for effective interactions with the translation machinery and other components of the SMN complex. Notably, its WD40 repeat domains and the TPR domains are essential for these interactions, influencing the recruitment and association of Gemin5 with ribosomes and impacting translational control.

The oligomerization status of Gemin5 distinctly affects its interactome. Proteins capable of oligomerization interact with ribosomal components and translation regulation factors more extensively than those lacking the oligomerization domains. These interactions enhance Gemin5’s role in regulating translation, where it can either promote or inhibit the translation process depending on the domain involved and its oligomerization state.

Additionally, the authors discuss how the loss of oligomerization impacts the protein’s interaction with SMN complex members, further illustrating the critical nature of Gemin5’s structural configuration in its functional roles. This relationship highlights a broader implication for Gemin5’s involvement in disease states, particularly neurological disorders, where its dysfunction may be linked to translational misregulation.

Overall, the study advances our understanding of how Gemin5’s structural domains orchestrate its diverse roles in cellular processes, particularly in translation regulation, through intricate interactions dictated by its oligomerization state.

Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots

Open Life Sciences, 2024

Jiang, P., Wang, X. and Wang, R.

Despite grape quality being crucial in wine production, some factors attributing to it are still lacking a comprehensive explanation. This study investigated the impact of different soil treatments on the quality of Cabernet Sauvignon grapevine roots and fruits using RNA-seq analysis, focusing on the molecular data linking these treatments to grape fruit quality. Three soil treatments were compared: inorganic fertilizer (NPK), organic fertilizer (Org), and a soil conditioner (SC).

RNA-seq analysis revealed significant differences in gene expression patterns of grapevine roots between the treatments. Notably, SC treatment led to a substantial modification in the transcriptional landscape compared to NPK and Org treatments. It also resulted in higher expression levels of key genes involved in anthocyanin biosynthesis, suggesting enhanced anthocyanin content in SC-treated grape fruits.

A weighted gene co-expression network analysis (WGCNA) identified specific gene modules correlated with biochemical indices of grape quality, such as soluble solids and anthocyanins. Five hub genes (ERF, JP, SF3B, UFGT1, UFGT3) were particularly associated with these traits, indicating their central role in the transcriptional response to soil conditioning. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) validation confirmed the upregulation of these genes in SC-treated roots, supporting the RNA-seq findings.

In summary, this study shows that soil conditioning significantly enhances grape fruit quality by altering gene transcription patterns in grapevine roots, providing a molecular basis for soil management strategies aimed at improving grape and wine quality.

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