Biology subjects

Munoz, J.

Publications and source records attributed to Munoz, J..

3 recordsLinked to original sources

bioRxiv2018

DNA and RNA binding mediate the toxicity of arginine-rich peptides encoded by C9ORF72 GGGGCC repeats

Due to their capability to transport chemicals or proteins into target cells, cell-penetrating peptides (CPPs) are being developed as therapy delivery tools. However, and despite their interesting properties, arginine-rich CPPs often show toxicity for reasons that remain poorly understood. Using a (PR)n dipeptide repeat that has been linked to amyotrophic-lateral sclerosis (ALS) as a model of an arginine-rich CPP, we here show that the presence of (PR)n leads to a generalized displacement of RNA- and DNA-binding proteins from chromatin and mRNA. Accordingly, any reaction involving nucleic acids such as RNA transcription, translation, splicing and degradation or DNA replication and repair are impaired by the presence of the CPP. Interestingly, the effects of (PR)n are fully mimicked by PROTAMINE, a small arginine-rich protein that displaces histones from chromatin during spermatogenesis. We propose that widespread coating of nucleic acids and consequent displacement of RNA- and DNA-binding factors from chromatin and mRNA accounts for the toxicity of arginine-rich CPPs, including those that have been recently associated to the onset of ALS.

neuroscience↗

bioRxiv2018

Exosomes are key regulators of non-cell autonomous communication in senescence

Senescence is a cellular phenotype characterized by an irreversible cell cycle arrest and the secretion of inflammatory proteins, denominated senescence-associated secretory phenotype (SASP). The SASP is important in influencing the behavior of neighboring cells and altering the microenvironment; yet, until now this role has been mainly attributed to soluble factors. Here, we report that extracellular vesicles also alter the environment by transmitting the senescent phenotype to other cells via exosomes (extracellular vesicles of endocytic origin). A combination of functional assays, Cre-/oxP reporter systems, proteomic analysis and RNAi screens confirm that exosomes form part of the senescent secretome and mediate paracrine senescence via the activation of a non-canonical interferon (IFN) pathway. Altogether, we speculate that exosomes could be drivers of tissue degeneration both locally and systemically during aging and age- related disease.

cell biology↗

bioRxiv2018

Seed predation increases from the Arctic to the Equator and from high to low elevations

Species interactions have long been predicted to increase in intensity towards the tropics and low elevations, due to gradients in climate, productivity, or biodiversity. Despite their importance for understanding global ecological and evolutionary processes, plant-animal interaction gradients are particularly difficult to test systematically across large geographic gradients, and evidence from smaller, disparate studies is inconclusive. By systematically measuring post-dispersal seed predation using 6980 standardized seed depots along 18 mountains in the Pacific cordillera, we found that seed predation increases 18% from the Arctic to Equator and 16% from 4000 masl to sea level. Clines in total predation, likely driven by invertebrates, were consistent across tree-line ecotones and in continuous forest, and were better explained by climate seasonality than by productivity, biodiversity, or latitude. These results suggest that species interactions play predictably greater ecological and evolutionary roles in tropical, lowland, and other less seasonal ecosystems.\n\nOne Sentence SummaryPost-dispersal seed predation increases from the Arctic to the Equator and from high elevations to sea level.

ecology↗