When Escherichia coli encounters stress, the endoribonuclease MazF initiates a post-transcriptional response that results in the reprogramming of protein synthesis. By removing the 3΄-terminus of the 16S rRNA, MazF generates specialized ribosomes that selectively translate mRNAs likewise processed by MazF. Given the energy required for de novo ribosome biosynthesis, we considered the existence of a repair mechanism operating upon stress relief to recycle the modified ribosomes. Here, we show that the stress-ribosomes and the 3΄-terminal 16S rRNA fragment are stable during adverse conditions. Moreover, employing in vitro and in vivo approaches we demonstrate that the RNA ligase RtcB catalyzes the re-ligation of the truncated 16S rRNA present in specialized ribosomes Thereby their ability to translate canonical mRNAs is fully restored. Together, our findings not only provide a physiological function for the RNA ligase RtcB in bacteria but highlight the reversibility of ribosome heterogeneity, a crucial but hitherto undescribed concept for translational regulation.
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http://dx.doi.org/10.1093/nar/gkw1018 | DOI Listing |
Biol Pharm Bull
December 2024
Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University.
We aimed to investigate the mechanism of high mobility group box 1 (HMGB1) in the accelerated fracture healing process during Traumatic brain injury (TBI). The lateral ventricles of mice in the TBI model group were injected with adenovirus-packaged short hairpin RNA (shRNA)-HMGB1 or overexpressing (ov)-HMGB1 vector. We found HMGB1 levels were higher in bone tissue at the fracture end of TBI combined with fracture model mice.
View Article and Find Full Text PDFBiochem Pharmacol
December 2024
Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361005, China; Xiamen Key Laboratory of Otolaryngology Head and Neck Surgery, Xiamen 361005, Fujian, China. Electronic address:
Our study had demonstrated that WW domain-binding protein 2 (WBP2) conferred chemoresistance in breast cancer (BC). However, the underlying mechanism remains unclear. Herein, a decreased expression of itchy E3 ubiquitin protein ligase (ITCH) was observed in drug-resistant BC tissues which negatively regulated the expression of WBP2.
View Article and Find Full Text PDFCell Death Dis
December 2024
State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing, 400715, China.
Chemoresistance poses a significant clinical challenge in the treatment of gastric cancer (GC), while its underlying molecular mechanisms are still not fully understood. Post-translational protein modification and abnormal activation of nuclear factor-kappa B (NF-κB) are critical regulators of tumor chemoresistance. This study investigates the role of TNF receptors-associated factors 6 (TRAF6) in 5-Fluorouracil (5-FU) resistant GC.
View Article and Find Full Text PDFCancer Commun (Lond)
December 2024
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, P. R. China.
Background: The majority of patients with prostate cancer (PCa) exhibit intrinsic resistance to immune checkpoint blockade (ICB) following radiotherapy (RT). This resistance is generally attributed to the limited antigen presentation of heterogeneous cells within tumors. Here, we aimed to isolate and characterize these diverse subgroups of tumor post-RT to understand the molecular mechanisms of their resistance to ICB.
View Article and Find Full Text PDFJ Immunother Cancer
December 2024
Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Background: Loss-of-function mutations of (, also termed as ()) are frequently detected in patients with non-small cell lung cancer (NSCLC). The mutant NSCLC was refractory to almost all the antitumor treatments, including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy. Unfortunately, mechanisms underlying resistance to immunotherapy are not fully understood.
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