Comprehensive profiling of small RNAs and their changes and linkages to mRNAs in schizophrenia and bipolar disorder

We investigated small non-coding RNAs (sncRNAs) from the prefrontal cortex of 93 individuals diagnosed with schizophrenia (SCZ) or bipolar disorder (BD) and 77 controls. We uncovered recurring complex sncRNA profiles, with 98% of all sncRNAs being accounted for by miRNA isoforms (60.6%), tRNA-derived fragments (17.8%), rRNA-derived fragments (11.4%), and Y RNA-derived fragments (8.3%). In SCZ, 15% of all sncRNAs exhibit statistically significant changes in their abundance. In BD, the fold changes (FCs) are highly correlated with those in SCZ but less acute. Non-templated nucleotide additions to the 3′-ends of many miRNA isoforms determine their FC independently of miRNA identity or genomic locus of origin. In both SCZ and BD, disease- and age-associated sncRNAs and mRNAs reveal accelerated aging. Co-expression modules between sncRNAs and mRNAs align with the polarities of SCZ changes and implicate sncRNAs in critical processes, including synaptic signaling, neurogenesis, memory, behavior, and cognition.