#RNA

doi.org

Pathogenic proteotoxicity of cryptic splicing is alleviated by ubiquitination and ER-phagy

RNA splicing enables the functional adaptation of cells to changing contexts. Impaired splicing has been associated with diseases, including retinitis pigmentosa, but the underlying molecular mechanis...

doi.org

Advancing global genomic equity: making a case for national genome projects in Africa | Nature Communications

Genomic data hold transformative potential for healthcare. Despite their unparalleled genetic diversity, African populations remain underrepresented in global genomics research, contributing to poorer health outcomes both within Africa and globally. Political, financial, and social challenges hinder progress, and therefore advocacy for public understanding of genomics, addressing social stigma, and aligning initiatives with national policies are critical steps forward. Africa hosts a large pool of highly skilled scientists and laboratories with DNA analysis capacity to harness for human genetics research and service provision, presenting opportunities for growth and innovation. This article highlights progress in African genomics, emphasizes the importance of equity, and proposes actionable steps for prioritizing, funding, and implementing national genome projects. It is a call to action. Genomic data could transform healthcare, but African populations are underrepresented, currently l

doi.org

Enhancing immunity during ageing by targeting interactions within the tissue environment | Nature Reviews Drug Discovery

Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as ‘inflammageing’. In this Review article, we highlight how the processes of inflammation and senescence drive each other, leading to loss of immune function. To break this cycle, therapies are needed that target the interactions between the altered tissue environment and the immune system instead of targeting each component alone. We discuss the relative merits and drawbacks of therapies that are directed at eliminating senescent cells (senolytics) and those that inhibit inflammation (senomorphics) in the context of tissue niches. Furthermore, we discuss therapeutic strategies designed to directly boost immune cell function and improve immune surveillance in tissue

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Cellular RNA interacts with MAVS to promote antiviral signaling

Antiviral signaling downstream of RIG-I–like receptors (RLRs) proceeds through a multi-protein complex organized around the adaptor protein mitochondrial antiviral signaling protein (MAVS). Protein co...

doi.org

Learning shapes neural geometry in the primate prefrontal cortex | Nature Neuroscience

The relationship between the geometry of neural representations and the task being performed is a central question in neuroscience. The primate prefrontal cortex (PFC) is a primary focus of inquiry, as it can encode information with geometries that either rely on past experience or are experience agnostic. One hypothesis is that PFC representations should evolve with learning, from a format that supports exploration of all possible task rules to a format that minimizes the encoding of task-irrelevant features and supports generalization. Here we test this idea by recording neural activity from the macaque PFC when learning a new rule (‘XOR rule’) from scratch. We show that PFC representations progress from being high dimensional, nonlinear and randomly mixed to low dimensional and rule selective. Upon generalizing the rule to new stimuli, these representations further evolve into an abstract, stimulus-invariant geometry. These findings reconcile previously conflicting accounts of PFC f

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New forms of life discovered inside human bodies

Researchers find obelisks, mysterious RNA molecules in human bacteria that challenge our understanding of viruses and microscopic life.

doi.org

Gut bacterial metabolite imidazole propionate potentiates Alzheimer’s disease pathology | Nature Communications

The gut microbiome modulates metabolic and neurovascular processes implicated in Alzheimer’s disease and related dementias (ADRD), but the underlying mechanisms remain unclear. Here, we identify the bacterial metabolite imidazole propionate (ImP) as a modifier of ADRD pathology. In a cohort of 1196 cognitively unimpaired adults, higher plasma ImP levels were associated with lower preclinical cognitive scores and biomarkers of ADRD, both cross-sectionally and longitudinally. Fecal metagenomic analysis linked putative ImP producers to ADRD phenotypes. Genome-wide integrative analysis revealed a locus on chromosome 12 associated with both plasma ImP levels and AD risk in humans, supporting a host genetic contribution to ImP regulation and a causal role of this metabolite in AD. In mice, chronic ImP administration exacerbated AD-like pathology. ImP impaired brain endothelial barrier and promoted tau hyperphosphorylation in primary neurons, an effect blocked by glycogen synthase kinase-3β i

www.biorxiv.org

Structure of an Archaeal Ribosome with a Divergent Active Site

The ribosome is the universal translator of the genetic code and is shared across all life. Despite divergence in ribosome structure over the course of evolution, the peptidyl transferase center (PTC)...