August 27th
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, Vijjamarri et al. look at the significance of Dhh1 and Pat1 in translational suppression in yeast, Zhang et al. investigate the role of maternal proteins in the conversion of gametes to embryos in mice, and finally Huang et al. look at the role of ethylene on rice.
mRNA decapping activators Pat1 and Dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability
Nucleic Acids Research, 2023
Vijjamarri, A.K., Gupta, N., Onu, C., Niu, X., Zhang, F., Kumar, R., Lin, Z., Greenberg, M.L. and Hinnebusch, A.G.
In this research study, the role of yeast mRNA decapping activators, Pat1 and Dhh1, and their contribution to the suppression of translation and levels of certain mRNAs in cells with ample nutrients was investigated. Tools such as ribosome profiling, RNA-Seq, CAGE analysis focusing on capped mRNAs, RNA Polymerase II ChIP-Seq, and TMT-mass spectrometry were utilised. Earlier findings which indicated that Pat1 and Dhh1 play partially overlapping roles in suppressing overall translation in cells deprived of glucose were taken into account as part of this study.
The authors examined a double mutant with both pat1Δ and dhh1Δ deletions, comparing these outcomes with previously gathered data from a dhh1Δ mutant grown under the same conditions. The research findings unveil a significant collaboration between Dhh1 and Pat1 in the regulation of mRNA levels. This collaboration predominantly revolves around the mediation of decapping by Dcp1/Dcp2 and the subsequent degradation of mRNAs, distinguishing it from indirect transcriptional reactions. The mRNAs subjected to this process generally demonstrate adequate translational activity and lack an enrichment of suboptimal codons, suggesting the operation of a more precise targeting mechanism. Additionally, the results illustrate how Pat1 cooperates with Dhh1 to inhibit the translation of specific mRNAs. Notably, a discovery has been made that Dhh1 and Pat1 synergistically operate in cells abundant with nutrients, preferentially suppressing the abundance or translation of mRNAs encoding proteins typically expressed solely in starved cells. This discovery underscores an added layer of post-transcriptional control, which complements the well-established transcriptional procedures in harmonizing gene expression with the availability of nutrients.
The study underscores the significance of Dhh1 and Pat1 as crucial regulators in adjusting gene expression based on the availability and quantity of essential nutrients.
Stable maternal proteins underlie distinct transcriptome, translatome, and proteome reprogramming during mouse oocyte-to-embryo transition
Genome Biology, 2023
Zhang, H., Ji, S., Zhang, K., Chen, Y., Ming, J., Kong, F., Wang, L., Wang, S., Zou, Z., Xiong, Z., Xu, K., Lin, Z., Huang, B., Liu, L., Fan, Q., Jin, S., Deng, H., & Xie, W.
During the oocyte-to-embryo transition, the conversion of gametes to embryo is controlled by maternal mRNAs and proteins, with genome activation occurring post-fertilisation, and the coordination of transcriptome, translatome, and proteome during this phase is not well comprehended.
Employing a sensitive LC–MS/MS method, the authors investigated mouse oocyte and early embryo proteomes, along with translatome and transcriptome relationships. Results revealed distinct gene expression shifts during oocyte maturation and embryo development. The transcriptome and translatome changes were notable at the 2-cell stage, while the most significant proteome alteration occurred between the 8-cell and blastocyst stages. Notably, fewer genes were dynamically regulated in the proteome (52.2%) compared to the translatome (83.5%) and transcriptome (80.8%) during oocyte-to-embryo transition (OET), attributed to proteins stockpiled in fully grown oocytes. Stable oocyte proteins may conserve energy for prolonged arrest and essential embryo functions. Conversely, translatome and transcriptome experiences considerable changes, some possibly unrelated to the proteome. Roughly 43% to 80% of protein variance can be explained by translation and transcription, while post-translational mechanisms might account for the rest.
To summarise, data integration from highly sensitive methodologies highlighted distinct dynamics in the proteome compared to the translatome and transcriptome during the mouse oocyte-to-embryo transition (OET). This research contributes to advancing our comprehension of mammalian OET and the underlying fundamental principles that regulate gene expression.
A translational regulator MHZ9 modulates ethylene signaling in rice
Nature Communications, 2023
Huang, Y.-H., Han, J.-Q., Ma, B., Cao, W.-Q., Li, X.-K., Xiong, Q., Zhao, H., Zhao, R., Zhang, X., Zhou, Y., Wei, W., Tao, J.-J., Zhang, W.-K., Qian, W., Chen, S.-Y., Yang, C., Yin, C.-C., & Zhang, J.-S.
Ethylene plays an important role in rice growth, development and stress tolerance. Translational control of ethylene signalling remains unclear in rice. The aim of this study was to delve into the ethylene response of rice using an ethylene-response mutant called mhz9. A number of techniques were employed in this study, including polysome profiling, ribosome profiling, RIP-seq, and CLIP-seq.
They identified a glycine-tyrosine-phenylalanine (GYF) domain protein named MHZ9 that interacts with OsEBF1/2 mRNA to positively regulate translation during rice’s ethylene response. The C-terminal domain of MHZ9 appears to connect with OsEIN2-C to receive upstream ethylene signals and then binds directly to OsEBF1/2 mRNA via its N-terminal domain, inhibiting translation in P-bodies. Interestingly, although P-bodies are typically sites of mRNA turnover and translational repression, MHZ9 binding to OsEBF1/2 mRNA in P-bodies seemed to increase mRNA stability and abundance rather than degradation.
Polysome profiling revealed that ethylene mildly repressed OsEBF1/2 mRNA translation, a process dependent on MHZ9. Various assays confirmed MHZ9’s role in the translational repression of OsEBF1/2 mRNA. The inhibition of OsEBF2 translation prevents the degradation of the transcription factor OsEIL1, leading to increased levels of OsEIL1 that activate downstream signalling. Ribo-seq analysis suggested that MHZ9 is required for the regulation of ~ 90% of genes translationally affected by ethylene.
The study concluded that MHZ9 serves as a translational regulator during rice’s ethylene response. It directly binds to OsEBF1/2 mRNAs and influences the translation of multiple genes in response to ethylene. It was suggested that MHZ9 may also have roles independent of ethylene, affecting genes beyond OsEBFs. This study opens new perspectives for understanding translational regulation in ethylene signaling and its potential agricultural applications.