August 4th, 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, Leow et al. underlined that the regulation of Water-Soluble Palm Fruit Extract improved insulin sensitivity, and therefore, attenuated the progression of diabetes and associated liver diseases. Zhang et al. stated that NSUN2 regulated HGH1 expression through m5C modification to alter the protein synthesis in breast cancer cells. Liu et al. used CRISPR/Cas9 technology to identify eIF(iso)4e.c as the key resistance genes in Brassica rapa to Turnip mosaic virus that causes crop diseases.

 

RNA-Seq transcriptome profiling of Nile rat livers reveals novel insights on the anti-diabetic mechanisms of Water-Soluble Palm Fruit Extract

Journal of Applied Genetics, 2024

Leow, S.S., Khoo, J.S., Lee, W.K., Hoh, C.C., Fairus, S., Sambanthamurthi, R. and Hayes, K.C.

The study aimed to investigate the anti-diabetic effects of Water-Soluble Palm Fruit Extract (WSPFE) on Nile rats (NRs), with a focus on the hepatic transcriptomic changes using next-generation RNA sequencing. The researchers compared the impacts of liquid and spray-dried powder forms of WSPFE when added to a high-carbohydrate diet. Additionally, they aimed to identify gene expression differences between diabetes-resistant and diabetes-susceptible NRs to better understand the genetic factors contributing to diabetes development. This research builds on previous studies but leverages more advanced genomic tools to provide deeper insights.

The findings revealed that both liquid and spray-dried powder forms of WSPFE delayed the onset of diabetes in NRs on a high-carbohydrate diet, with the liquid form offering better protection. RNA sequencing analysis showed that WSPFE upregulated genes related to insulin sensitivity and hepatic metabolism while downregulating those associated with inflammation and liver disease. These results suggest that WSPFE enhances insulin sensitivity and reduces inflammation, thereby inhibiting the progression of diabetes and liver disease in NRs. Furthermore, the study identified gene expression differences between diabetes-resistant and diabetes-susceptible NRs, providing insights into the genetic factors influencing diabetes development.

Translatomic tools, such as RNA sequencing, were crucial in advancing our knowledge by revealing specific gene expression changes linked to WSPFE’s anti-diabetic effects. This advanced genomic technique allowed researchers to identify the genetic mechanisms through which WSPFE exerts its beneficial effects, offering a more detailed understanding of its role in preventing diabetes and associated liver diseases.

NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation

Breast Cancer Research, 2024

Zhang, X., An, K., Ge, X., Sun, Y., Wei, J., Ren, W., Wang, H., Wang, Y., Du, Y., He, L. and Li, O.

RNA m5C methylation is known to play a significant role in tumour initiation and progression, with NSUN2 identified as a pivotal enzyme involved in this process across various cancer types. Driven by the rising incidence of breast cancer and the existing limitations in current diagnostic and therapeutic methods, the role of NSUN2-mediated m5C RNA methylation in breast cancer was investigated. The study aimed to uncover the molecular mechanisms through which NSUN2 regulates the expression of HGH1, a newly identified target gene in breast cancer, via m5C modification. By employing RNA-seq and other analytical techniques, the researchers sought to elucidate how NSUN2 and its interaction with YBX1 contribute to the stability and expression of HGH1, thus influencing breast cancer progression.

From RNA-seq analyses, HGH1 emerged as a key target of dysregulated m5C modifications in breast cancer. The findings demonstrated that NSUN2 and YBX1 collaboratively enhance the mRNA stability of HGH1, thereby promoting its overexpression and the aggressive progression of breast cancer. Additionally, using proteomics and translation sequencing experiments, the study revealed a novel interaction between HGH1 and the translation elongation factor EEF2, which significantly enhances protein translation efficiency in breast cancer cells. These results provide a comprehensive understanding of the intricate mechanisms by which NSUN2-mediated m5C modification drives oncogenic processes in breast cancer.

This research underscores the critical involvement of RNA m5C modification in tumor development, highlighting NSUN2 and HGH1 as potential therapeutic targets for breast cancer. By elucidating the pathways through which these molecules regulate gene expression and protein synthesis, this study paves the way for targeted therapies aimed at disrupting these processes to mitigate breast cancer progression and improve patient outcomes.

Editing of eIF(iso)4E.c confers resistance against Turnip mosaic virus in Brassica rapa

Horticultural Plant Journal, 2024

Liu, Y., Xin, X., Li, P., Wang, W., Yu, Y., Zhao, X., Zhang, D., Wang, J., Zhang, F., Zhang, S. and Yu, S.

Chinese cabbage, also known as Brassica rapa, is a crucial vegetable crop from China. However, Turnip mosaic virus (TuMV) severely affects its production, causing significant crop losses globally. Efforts to combat TuMV include cloning resistance genes and studying molecular mechanisms. Recent studies highlight plant translation initiation factors eIF4E and eIF4G as critical for recessive disease resistance. In this study, the authors aim to identify and validate resistance genes in Chinese cabbage against TuMV using CRISPR/Cas9 and sequencing technologies like ribosome profiling and RNA sequencing, to enhance understanding of resistance mechanisms, improve breeding programs, and reduce crop losses.

Recessive genes are crucial for breeding disease-resistant crops, with eIF4E family members playing key roles in antiviral defence. The study used CRISPR/Cas9 to create eif(iso)4e.c mutants in Brassica rapa, confirming their resistance to TuMV through phenotypic and virus content evaluations. Ribosome profiling and RNA sequencing revealed that eIF(iso)4E.c regulates gene expression at both transcriptional and translational levels. Comparative analysis showed that eIF(iso)4E.c impacts disease resistance pathways, including plant-pathogen interaction and MAPK signalling, highlighting the importance of translation efficiency in antiviral defence mechanisms.

This study validated eIF(iso)4E.c as a key gene in Brassica rapa’s resistance to TuMV. Translatomic techniques revealed role of eIF(iso)4E.c in regulating disease resistance at both transcriptional and translational levels, enhancing understanding of plant-virus interactions. This knowledge can be applied to develop more effective, resistant crop varieties through targeted breeding programs and genetic engineering, ultimately reducing crop losses and improving food security.

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