HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III.

Molecular chaperones are critical for protein homeostasis and are implicated in several human pathologies such as neurodegeneration and cancer. While the binding of chaperones to nascent and misfolded proteins has been studied in great detail, the direct interaction between chaperones and RNA has not been systematically investigated. Here, we provide the evidence for widespread interaction between chaperones and RNA in human cells. We show that the major chaperone heat shock protein 70 (HSP70) binds to non-coding RNA transcribed by RNA polymerase III (RNA Pol III) such as tRNA and 5S rRNA. Global chromatin profiling revealed that HSP70 binds genomic sites of transcription by RNA Pol III. Detailed biochemical analyses showed that HSP70 alleviates the inhibitory effect of cognate tRNA transcript on tRNA gene transcription. Thus, our study uncovers an unexpected role of HSP70-RNA interaction in the biogenesis of a specific class of non-coding RNA with wider implications in cancer therapeutics.

Molecular Highway Patrol for Ribosome Collisions.

During translation, messenger RNAs (mRNAs) are decoded by ribosomes which can stall for various reasons. These include chemical damage, codon composition, starvation, or translation inhibition. Trailing ribosomes can collide with stalled ribosomes, potentially leading to dysfunctional or toxic proteins. Such aberrant proteins can form aggregates and favor diseases, especially neurodegeneration. To prevent this, both eukaryotes and bacteria have evolved different pathways to remove faulty nascent peptides, mRNAs and defective ribosomes from the collided complex. In eukaryotes, ubiquitin ligases play central roles in triggering downstream responses and several complexes have been characterized that split affected ribosomes and facilitate degradation of the various components. As collided ribosomes signal translation stress to affected cells, in eukaryotes additional stress response pathways are triggered when collisions are sensed. These pathways inhibit translation and modulate cell survival and immune responses. Here, we summarize the current state of knowledge about rescue and stress response pathways triggered by ribosome collisions.

Projections of the Diencephalospinal Dopaminergic System to Peripheral Sense Organs in Larval Zebrafish (Danio rerio).

Dopaminergic neurons of the descending diencephalospinal system are located in the posterior tuberculum (PT) in zebrafish (Danio rerio), and correspond in mammals to the A11 group in hypothalamus and thalamus. In the larval zebrafish, they are likely the only source of central dopaminergic projections to the periphery. Here, we characterized posterior tubercular dopaminergic fibers projecting to peripheral sense organs, with a focus on the lateral line neuromasts. We labeled and identified catecholaminergic neurons and their projections by combining two immunofluorescence techniques, (i) using an antibody against Tyrosine hydroxylase, and (ii) using an antibody against GFP in transgenic zebrafish expressing in catecholaminergic neurons either membrane-anchored GFP to track fibers, or a Synaptophysin-GFP fusion to visualize putative synapses. We applied the CLARITY method to 6 days old whole zebrafish larvae to stain and analyze dopaminergic projections by confocal microscopy. We found that all lateral line neuromasts receive direct innervation by posterior tubercular dopaminergic neurons, and tracked these projections in detail. In addition, we found dopaminergic fibers projecting to the anterior and posterior lateral line ganglia, and extensive central dopaminergic arborizations around the terminal projection field of the lateral line afferent neurons in the hindbrain medial octavolateralis nucleus (MON). Therefore, dopaminergic innervation may affect lateral line sense information at different processing stages. Additional dopaminergic fibers innervate the trigeminal ganglion, and we observed fine catecholaminergic fibers in the skin with arborization patterns similar to free sensory nerve endings. We also detected potentially dopaminergic fibers innervating inner ear sensory epithelia. Therefore, the diencephalospinal A11-type dopaminergic system may broadly modulate peripheral senses. We also briefly report peripheral sympathetic catecholaminergic projections labeled in our experiments, and their innervation of the developing intestine, swim bladder and abdominal organs.