April 13th, 2025
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,
- Bujisic et al. highlight a coordinated mechanism where 7SL RNA and SRP function together to shut down gene expression.
- Lyu et al. perform ribosome profiling on species of the Flaveria genus and uncover regulatory mechanisms that enhance C4 gene expression.
- Yao et al. investigate how 5’UTRs regulate gene expression in the unconventional yeast Komagataella phaffii.
7SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stress
Nature Communications, 2025
Bujisic, B., Lee, H.G., Xu, L., Weissbein, U., Rivera, C., Topisirovic, I. and Lee, J.T.
This paper explores the novel function of 7SL RNA and the signal recognition particle (SRP) beyond protein translocation. The study provides evidence for 7SL RNA and SRP mediating a global response to acute heat shock by regulating transcription and translation across the nucleus, cytosol, and mitochondria. Using advanced techniques like ribosome profiling (Ribo-Seq) and chromatin binding assays, the authors demonstrate that—upon acute thermal stress—SRP interacts with ribosomes and inhibits translation, particularly targeting nuclear-encoded mitochondrial mRNAs, while 7SL RNA is upregulated, accumulates in the nucleus, and binds chromatin to suppress transcription. Notably, the suppression is independent of signal peptides. The paper highlights a coordinated mechanism where 7SL RNA and SRP function together to shut down gene expression, conserving cellular resources and modulating the stress response across multiple cellular compartments.
Ribosome profiling highlights the selective translational suppression is heat shock-specific and that knockdown of SRP components (SRP54/SRP72) restores protein synthesis and enhances cell survival under heat stress. Cluster analysis of ribosome-protected fragments (RPFs) identifies a distinct subset of mRNAs particularly sensitive to SRP-dependent suppression, primarily involved in mitochondrial function and metabolism. These results suggest that SRP selectively targets specific translation programs during stress, rather than acting as a general inhibitor. This insight opens new avenues for studying SRP in stress responses and potential therapeutic applications, particularly in diseases linked to protein homeostasis, such as neurodegeneration and cancer.
Learn more about EIRNA Bio’s ribosome profiling service here.
A dominant role of transcriptional regulation during the evolution of C4 photosynthesis in Flaveria species
Nature Communications, 2025
Lyu, M.J.A., Du, H., Yao, H., Zhang, Z., Chen, G., Huang, Y., Ni, X., Chen, F., Zhao, Y.Y., Tang, Q., Miao, F. et al.
C4 photosynthesis is more efficient than C3 photosynthesis in terms of light, water, and nitrogen use, but the mechanisms of the evolutionary transition between the two systems is not well understood. Through the use of chromosome-scale genomic assemblies and subsequent analysis of transcriptomic, proteomic, and ribosome profiling data from species of the Flaveria genus, this study elucidates regulatory mechanisms that enhance C4 gene expression, and highlights the evolutionary pathway that contributed to C4 evolution. The study identifies that C4 genes exhibit significantly higher transcript abundance relative to C3 and C3-C4 counterparts, as well as key transcription factors, such as the ethylene response factor transcription factors and the associated cis-regulatory elements.
Ribosome profiling, conducted on C3 and C4 species, demonstrated that translational efficiency between photosynthetic systems is comparable. Analysis of ribosome-protected fragments (RPFs) showed strong correlation between RNA abundance and ribosome occupancy, revealing that transcription, rather than translation, is the primary regulatory factor affecting C4 gene expression. This result is supported by protein-to-RPF ratios in C4 species being lower than in C3 species. The conclusion of the results is that, as regulation of translation is similar between C3 and C4 species, transcriptional regulation must be a key driver to C4 evolution. These findings implicate that the engineering of C4 trains into C3 crops for higher produce yield, may require enhanced transcriptional elements support improving the photosynthetic efficiency.
Learn more about EIRNA Bio’s ribosome profiling service here.
Nucleotide distribution analysis of 5′UTRs in genome-scale directs their redesign and expression regulation in yeast
Metabolic Engineering, 2025
Yao, C., Yin, Y., Li, Q., Zhang, H., Zhang, Y., Shao, Q., Liu, Q., Ren, Y. and Cai, M.
In this paper, the authors investigated how 5’ untranslated regions (5’UTRs) regulate gene expression in the unconventional yeast Komagataella phaffii. The study identified that a decreasing frequency of guanine in the -100 to -1 region of 5’UTRs, suggesting a relationship with translation efficiency. Synthetic 5’UTRs were engineered by replacing guanines with adenine or thymine in the specific -100 to -1 region. In particular, a triplet motif at the -3 to -1 region, termed KZ3, was observed to act as a key determinant to significantly enhance gene expression. A primary focus of the study was in the evaluation of 128 engineered KZ3 variants with methanol-inducible and constitute promoters.
Polysome profiling was used to determine how the engineered 5’UTRs influenced translation. Polysome profiling analysis was compared with real-time quantitative PCR data to reveal the fact that transcription levels were not altered by the engineered 5’UTRs, but significantly increased ribosome recruitment to target mRNAs. Additional experiments with fluorescent reporters confirmed that increased protein levels were due to translational enhancement rather than transcriptional upregulation. Of the engineered KZ3 variants, 58 were confirmed to enhance gene expression, with some having an observed 15-fold increase. These findings provide novel tools for fine-tuning gene expression in yeast, including unconventional strains, with wide-reaching applications in metabolic engineering and synthetic biology.
Learn more about EIRNA Bio’s polysome profiling service here.