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Yale study tracks protein across human brain

November 28, 2017

Yale Department of Psychiatry researchers reported an extensive survey of protein abundance across the human brain in the December issue of Nature Neuroscience.

The data extends RNA-based gene expression atlases and highlights that proteins levels in different brain regions vary more than suggested by their mRNA abundances.

This was particularly apparent within the neocortex, where there is a large variability in the expression of membrane–associated proteins that was not predictable via their mRNA abundance, including the metabotropic glutamate receptor 2/3 (mGluR2/3) and the cannabinoid 1 (CB1) receptor.

"A variety of techniques allow us to measure the activity of each gene, including epigenetic and RNA profiling, however none come as close to the true 'output' of the gene as a direct measurement of the protein it produces," said Becky Carlyle, PhD, lead author of the study and former Associate Research Scientist at Yale. "We're excited about this new resource because we believe it will help shed new light on the complex relationship between the genome and the structure and function of the brain."

The findings highlight that post-transcriptional regulation of gene expression is complex in brain tissue, with the production, localization, and turnover of proteins contributing to larger variations in expression between brain regions than would be expected by profiling mRNA levels in the same tissue.

"It is thanks to the extremely high quality tissue procurement and archiving at Yale that we were are able to profile both protein and mRNA from exactly the same tissue and perform such an integrated analysis" said Robert Kitchen, PhD, co-lead author and a former Postdoctural Associate at Yale.

The team of Yale researchers led by Carlyle; Kitchen; Angus Nairn, PhD, Charles B. G. Murphy Professor of Psychiatry; and Nenad Sestan, MD, PhD, Professor of Neuroscience, of Comparative Medicine, of Genetics and of Psychiatry, have made all data and results in this study available as a resource.

"It is our hope that this is the first of many insights as other researchers mine this vast dataset to inform their own hypotheses and that more neuroscientists will be encouraged to adopt proteomics as part of their standard experimental techniques," Carlyle said.

Submitted by Christopher Gardner on November 27, 2017