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The Liminal Space
Systematic analysis of YFP traps reveals common mRNA/protein discordance in neural tissues.
While post-transcriptional control is thought to be required at the periphery of neurons and glia, its extent is unclear. Here, we investigate systematically the spatial distribution and expression of mRNA at single molecule sensitivity and their corresponding proteins of 200 YFP trap lines across the intact Drosophila…
Addendum: Precise tuning of gene expression levels in mammalian cells.
Following re-sequencing of the miSFIT constructs used in the paper, two of the construct variants inserted into the 3'UTR of PD-1, namely '12C' and '17A, 18G', have been found to contain additional insertions not present in the other construct variants. The data points corresponding to these constructs in Figs.…
Dynamically regulated transcription factors are encoded by highly unstable mRNAs in the Drosophila larval brain.
The level of each RNA species depends on the balance between its rates of production and decay. Although previous studies have measured RNA decay across the genome in tissue culture and single-celled organisms, few experiments have been performed in intact complex tissues and organs. It is therefor…
Ribo-Pop: simple, cost-effective, and widely applicable ribosomal RNA depletion.
The measurement of RNA abundance derived from massively parallel sequencing experiments is an essential technique. Methods that reduce ribosomal RNA levels are usually required prior to sequencing library construction because ribosomal RNA typically comprises the vast majority of a total RNA sample. For…
mRNA length-sensing in eukaryotic translation: reconsidering the "closed loop" and its implications for translational control.
Most eukaryotic mRNAs are recruited to the ribosome by recognition of a 5' m7GpppN cap. 30 years of genetic and biochemical evidence point to a role for interaction between the 5' cap-interacting factors and the 3' poly(A)-binding protein in bringing the ends of the mRNA into close proximity and promoting bo…
Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans.
The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may serve regulatory rol…
The ribosomal protein Asc1/RACK1 is required for efficient translation of short mRNAs.
Translation is a core cellular process carried out by a highly conserved macromolecular machine, the ribosome. There has been remarkable evolutionary adaptation of this machine through the addition of eukaryote-specific ribosomal proteins whose individual effects on ribosome function are largely unknown…
Protein kinase A regulates gene-specific translational adaptation in differentiating yeast.
Cellular differentiation is driven by coordinately regulated changes in gene expression. Recent discoveries suggest that translation contributes as much as transcription to regulating protein abundance, but the role of translational regulation in cellular differentiation is largely unexplored. Here we investigate tra…
Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences.
Despite an unprecedented global research effort on SARS-CoV-2, early replication events remain poorly understood. Given the clinical importance of emergent viral variants with increased transmission, there is an urgent need to understand the early stages of viral replication and transcription. We used si…
Precise tuning of gene expression levels in mammalian cells.
Precise, analogue regulation of gene expression is critical for cellular function in mammals. In contrast, widely employed experimental and therapeutic approaches such as knock-in/out strategies are more suitable for binary control of gene activity. Here we report on a method for precise control of gene ex…
Emerging gene therapies for cystic fibrosis.
Introduction: Cystic fibrosis (CF) remains a life-threatening genetic disease, with few clinically effective treatment options. Gene therapy and gene editing strategies offer the potential for a one-time CF cure, irrespective of the CFTR mutation class. Areas covered: We review emerging gene therapies and gene…
Progress in Respiratory Gene Therapy.
The prospect of gene therapy for inherited and acquired respiratory disease has energized the research community since the 1980s, with cystic fibrosis, as a monogenic disorder, driving early efforts to develop effective strategies. The fact that there are still no approved gene therapy products for the lung, despit…
Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice.
SARS-CoV-2 is a newly emerged coronavirus, causing the global pandemic of respiratory coronavirus disease (COVID-19). The type I interferon (IFN) pathway is of particular importance for anti-viral defense and recent studies identified that type I IFNs drive early inflammatory responses to SARS-CoV-2. Here, we…
Prevention and management of venous thromboembolism
Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), has an incidence of about 1 per 1000 per annum, with two-thirds presenting as DVT and one-third as PE. Approximately half of VTEs are associated with hospital admissions, and hospital VTE preven…
Array Genotyping of Transfusion Relevant Blood Cell Antigens in 6946 Ancestrally Diverse Subjects.
Blood transfusions save millions of lives worldwide each year, yet formation of antibodies against non-self antigens remains a significant problem, particularly in frequently transfused patients. We designed and tested the Universal Blood Donor Typing (UBDT_PC1) array for automated high-throughput simultaneous…
In Vivo Visualization of Charcot-Bouchard Aneurysms on Lenticulostriate Arteries Using 7T MRI.
Background and purposeCharcot-Bouchard aneurysms (CBAs) are tiny aneurysms arising from small perforating arteries. Despite the potentially catastrophic consequences of rupture of these aneurysms, the existence and prevalence of CBAs are controversial. The literature in this area is sparse with most previo…
Adverse right ventricular remodelling, function, and stress responses in obesity: insights from cardiovascular magnetic resonance.
AIMS: We aimed to determine the effect of increasing body weight upon right ventricular (RV) volumes, energetics, systolic function, and stress responses using cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: We first determined the effects of World Health Organization class III obesity [bo…
Obesity in the absence of comorbidities is not related to clinically meaningful left ventricular hypertrophy.
Obesity is associated with the development of left ventricular (LV) hypertrophy. Whether obesity in in the absence of comorbidities can cause LV hypertrophy to an extent which could create diagnostic uncertainty with pathological states (such as hypertrophic cardiomyopathy) is unknown. We used cine cardiovasc…
Tumor-specific CD8 T cell characterization in HR+ breast cancer reveals an impaired antitumoral response in patients with lymph node metastasis.
Most breast cancers express the estrogen receptor (ER), but the immune response of hormone receptor-positive (HR+) breast cancer remains poorly characterized. Here, dendritic cells loaded with tumor lysate are used to identify tumor-reactive CD8 T cells, which are detected in most HR+ breast cancer…