Although it is universally accepted that protein synthesis occurs in the cytoplasm, the possibility that translation can also take place in the nucleus has been hotly debated. Reports have been published claiming to demonstrate nuclear translation, but alternative explanations for these results have not been excluded, and other experiments argue against it. Much of the appeal of nuclear translation is that functional proofreading of newly made mRNAs in the nucleus would provide an efficient way to monitor mRNAs for the presence of premature termination codons, thereby avoiding the synthesis of deleterious proteins. mRNAs that are still in the nucleus-associated fraction of cells are subject to translational proofreading resulting in nonsense-mediated mRNA decay and perhaps nonsense-associated alternate splicing. However, these mRNAs are likely to be in the perinuclear cytoplasm rather than within the nucleus. Therefore, in the absence of additional evidence, we conclude that nuclear translation is unlikely to occur.
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http://dx.doi.org/10.1016/j.ceb.2004.03.006 | DOI Listing |
Nat Commun
December 2024
Department of Biochemistry, McGill University, Montreal, QC, Canada.
Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal cord motor neurons of mouse and human origin localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress.
View Article and Find Full Text PDFNat Commun
December 2024
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China.
Human ANP32A/B (huANP32A/B) poorly support the polymerase activity of avian influenza viruses (AIVs), thereby limiting interspecies transmission of AIVs from birds to humans. The SUMO-interacting motif (SIM) within NS2 promotes the adaptation of AIV polymerase to huANP32A/B via a yet undisclosed mechanism. Here we show that huANP32A/B are SUMOylated by the E3 SUMO ligase PIAS2α, and deSUMOylated by SENP1.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
PROTACs have emerged as a therapeutic modality for the targeted degradation of proteins of interest (POIs). Central to PROTAC technology are the E3 ligase recruiters, yet only a few of them have been identified due to the lack of ligandable pockets in ligases, especially among single-subunit ligases. We propose that binders of partner proteins of single-subunit ligases could be repurposed as new ligase recruiters.
View Article and Find Full Text PDFMov Disord
December 2024
Department of Metabolomics, Corewell Health Research Institute, Royal Oak, Michigan, USA.
Background: Lewy body diseases, including dementia with Lewy bodies (DLB), are characterized by α-synuclein accumulation, leading to dementia. Previous studies suggest distinct epigenetic and metabolomic profiles in DLB.
Objective: This study aims to identify diagnostic biomarkers by analyzing the methylome and metabolome in the Brodmann area 7 of postmortem brain tissues from DLB patients and control subjects using multiomics approaches.
ACS Cent Sci
December 2024
Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Over 90% of cancer patients succumb to metastasis, yet conventional frontline therapy struggles to halt the progression of metastatic tumors. Targeted radionuclide therapy, which delivers radiation precisely to tumor sites, shows promise for treating metastasis. The rational design of a prodrug activation platform using radionuclides would be an ideal approach to synergize chemotherapy with targeted radionuclide therapy, yet it has not been established.
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