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1. Sexual stage–specific A-to-I mRNA editing is mediated by tRNA-editing enzymes in fungi

   https://doi.org/10.1073/pnas.2319235121  

   Bian, Zhuyun; Wang, Zeyi; Wang, Diwen; Xu, Jin-Rong (March 2024, Proceedings of the National Academy of Sciences)

   A-to-I RNA editing catalyzed by adenosine-deaminase-acting-on-RNA (ADARs) was assumed to be unique to metazoans because fungi and plants lack ADAR homologs. However, genome-wide messenger RNA (mRNA) editing was found to occur specifically during sexual reproduction in filamentous ascomycetes. Because systematic characterization of adenosine/cytosine deaminase genes has implicated the involvement ofTAD2andTAD3orthologs in A-to-I editing, in this study, we used genetic and biochemical approaches to characterize the role ofFgTAD2, an essential adenosine-deaminase-acting-on-tRNA (ADAT) gene, in mRNA editing inFusarium graminearum.FgTAD2had a sexual-stage-specific isoform and formed heterodimers with enzymatically inactiveFgTAD3. Using a repeat-induced point (RIP) mutation approach, we identified 17 mutations inFgTAD2that affected mRNA editing during sexual reproduction but had no effect on transfer RNA (tRNA) editing and vegetative growth. The functional importance of the H352Y and Q375*(nonsense) mutations in sexual reproduction and mRNA editing were confirmed by introducing specific point mutations into the endogenousFgTAD2allele in the wild type. An in vitro assay was developed to show that FgTad2-His proteins purified from perithecia, but not from vegetative hyphae, had mRNA editing activities. Moreover, the H352Y mutation affected the enzymatic activity of FgTad2 to edit mRNA but had no effect on its ADAT activity. We also identified proteins co-purified with FgTad2-His by mass spectrometry analysis and found that two of them have the RNA recognition motif. Taken together, genetic and biochemical data from this study demonstrated that FgTad2, an ADAT, catalyzes A-to-I mRNA editing with the stage-specific isoform and cofactors during sexual reproduction in fungi. 

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2. Combinatorial design of siloxane-incorporated lipid nanoparticles augments intracellular processing for tissue-specific mRNA therapeutic delivery

   https://doi.org/10.1038/s41565-024-01747-6  

   Xue, Lulu; Zhao, Gan; Gong, Ningqiang; Han, Xuexiang; Shepherd, Sarah J; Xiong, Xinhong; Xiao, Zebin; Palanki, Rohan; Xu, Junchao; Swingle, Kelsey L; et al (January 2025, Nature Nanotechnology)
3. Prevent and Reverse Metabolic Dysfunction-Associated Steatohepatitis and Hepatic Fibrosis via mRNA-Mediated Liver-Specific Antibody Therapy

   https://doi.org/10.1021/acsnano.4c13404  

   Zhang, Chenshuang; Teng, Yilong; Bai, Xin; Tang, Maoping; Stewart, William; Chen, Jake Jinkun; Xu, Xiaoyang; Zhang, Xue-Qing (December 2024, ACS Nano)
4. RNA polymerase II dynamics and mRNA stability feedback scale mRNA amounts with cell size

   https://doi.org/10.1016/j.cell.2023.10.012  

   Swaffer, Matthew P.; Marinov, Georgi K.; Zheng, Huan; Fuentes Valenzuela, Lucas; Tsui, Crystal Yee; Jones, Andrew W.; Greenwood, Jessica; Kundaje, Anshul; Greenleaf, William J.; Reyes-Lamothe, Rodrigo; et al (November 2023, Cell)
5. RNA polymerase II dynamics and mRNA stability feedback determine mRNA scaling with cell size

   https://doi.org/10.1101/2021.09.20.461005  

   Swaffer, M.P.; Marinov, G.K.; Zheng, H.; Jones, A.W.; Greenwood, J.; Kundaje, A.; Snijders, A.P.; Greenleaf, W.J.; Reyes-Lamothe, R.; Skotheim, J.M. (September 2021, bioRxiv)

   null (Ed.)

   A defining feature of cellular growth is that protein and mRNA amounts scale with cell size so that concentrations remain approximately constant, thereby ensuring similar reaction rates and efficient biosynthesis. A key component of this biosynthetic scaling is the scaling of mRNA amounts with cell size, which occurs even among cells with the same DNA template copy number. Here, we identify RNA polymerase II as a major limiting factor increasing transcription with cell size. Other components of the transcriptional machinery are only minimally limiting and the chromatin environment is largely invariant with size. However, RNA polymerase II activity does not increase in direct proportion to cell size, inconsistent with previously proposed DNA-titration models. Instead, our data support a dynamic equilibrium model where the rate of polymerase loading is proportional to the unengaged nucleoplasmic polymerase concentration. This sublinear transcriptional increase is then balanced by a compensatory increase in mRNA stability as cells get larger. Taken together, our results show how limiting RNA polymerase II and feedback on mRNA stability work in concert to ensure the precise scaling of mRNA amounts across the physiological cell size range. 

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