The valine-arginine dipeptide repeat protein encoded by mammalian telomeric RNA appears highly expressed in mitosis and may repress global translation.

Translation of mammalian telomeric G-rich RNA via the Repeat Associated non-AUG translation mechanism can produce two dipeptide repeat proteins: repeating valine-arginine (VR) and repeating glycine-leucine (GL). Their potentially toxic nature suggests that one or both must play a needed role in the cell. Using light microscopy combined with antibody staining we discovered that cultured human cells stain brightly for VR during mitosis with VR staining co-localizing with ribosomes. In vitro , VR protein represses translation in a firefly luciferase assay. Affinity purification combined with mass spectrometry identified ribosomal proteins as the major class of VR interacting proteins. Extension to mouse embryonic cerebral cortical development showed strong staining in the ventricular zone where high mitotic index neural progenitor cells proliferate and in the cortical plate where new neurons settle. These observations point to VR playing a key role in mitosis very possibly depressing global translation, a role mediated by the telomere. Teaser: The telomeric valine-arginine dipeptide repeat protein is highly expressed in mitotic cells in culture and in mouse embryonic neural tissue.

Mapping of neuronal and glial primary cilia contactome and connectome in the human cerebral cortex.

Primary cilia act as antenna receivers of environmental signals and enable effective neuronal or glial responses. Disruption of their function is associated with circuit disorders. To understand the signals these cilia receive, we comprehensively mapped cilia's contacts within the human cortical connectome using serial-section EM reconstruction of a 1 mm3 cortical volume, spanning the entire cortical thickness. We mapped the "contactome" of cilia emerging from neurons and astrocytes in every cortical layer. Depending on the layer and cell type, cilia make distinct patterns of contact. Primary cilia display cell-type- and layer-specific variations in size, shape, and microtubule axoneme core, which may affect their signaling competencies. Neuronal cilia are intrinsic components of a subset of cortical synapses and thus a part of the connectome. This diversity in the structure, contactome, and connectome of primary cilia endows each neuron or glial cell with a unique barcode of access to the surrounding neural circuitry.