Study Finds Altered RNA Editing in Schizophrenia

In Science Advances, a University of California at Los Angeles-led team takes a look at RNA editing and mitochondrial changes suspected of contributing to schizophrenia. Based on RNA sequencing, single-cell RNA-seq, reporter assays, and other analyses of post-mortem frontal cortex brain samples from individuals with or without schizophrenia from the PsychENCODE consortium cohort, the researchers mapped schizophrenia-associated RNA editome patterns. They highlighted differentially edited sites in the genome that tended to fall at 3' untranslated regions in the nuclear genome that affect mitochondrial functions. In schizophrenia-affected individuals of European ancestry, who were overrepresented in the study, the authors saw lower-than-usual RNA editing at these sites compared to the RNA editome found in control individuals, for example, while RNA editing appeared to be enhanced at these sites in post-mortem brain samples from African-American individuals with schizophrenia. "Together, this work present explicit evidence of the robust hypoediting trend in Europeans with [schizophrenia] and supports the functional relevance of RNA editing in nuclear-encoded mitochondrial genes," the authors report, adding that the study "provides an extensive characterization of RNA editing in [schizophrenia] and supplies valuable insight into the roles of dysregulated editing in mitochondrial function."