An OMA1 redox site controls mitochondrial homeostasis, sarcoma growth, and immunogenicity.

Aggressive tumors often display mitochondrial dysfunction. Upon oxidative stress, mitochondria undergo fission through OMA1-mediated cleavage of the fusion effector OPA1. In yeast, a redox-sensing switch participates in OMA1 activation.

MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration.

The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPT mRNA internal ribosome entry site. MAPT encodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules.

Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth.

Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore the therapeutic potential of targeting mitochondrial translation and report the results of high-content screening with putative blockers of mitochondrial ribosomes.

Structural basis of mitochondrial translation.

Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report ~3.

Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood.

Background: Extracellular vesicles (EVs) are secreted membranous particles intensively studied for their potential cargo of diagnostic markers. Efficient and cost-effective isolation methods need to be established for the reproducible and high-throughput study of EVs in the clinical practice.

Methods: We designed the nickel-based isolation (NBI) to rapidly isolate EVs and combined it with newly-designed amplified luminescent proximity homogeneous assay or digital PCR to detect biomarkers of clinical utility.

Studying the Translatome with Polysome Profiling.

Polysome fractionation by sucrose density gradient centrifugation followed by analysis of RNA and protein is a technique that allows to understand the changes in translation of individual mRNAs as well as genome-wide effects on the translatome. Here, we describe the polysome profiling technique and RNA as well as protein isolation procedures from sucrose fractions.

Molecular portraits: the evolution of the concept of transcriptome-based cancer signatures.

Cancer results from dysregulation of multiple steps of gene expression programs. We review how transcriptome profiling has been widely explored for cancer classification and biomarker discovery but resulted in limited clinical impact. Therefore, we discuss alternative and complementary omics approaches.