We observed that alcohol affected the expression of lncRNAs in all four brain regions (Table 2). Affected lncRNAs were represented by antisense lncRNAs, long intergenic noncoding RNAs (lincRNAs), and pseudogenes, at an approximately equal ratio. As lncRNA is known to be associated with splicing10–12, we set out to define the ontology of these affected lncRNAs. Major molecular functions were determined for each lncRNA, and integrative analysis revealed the functional relation of AUD-induced changes in lncRNAome to splicing and RNA processing (Table 3).Table 2Long noncoding RNAs altered in alcohol use disorder.TypeSymbolFCFDRSFClincRNASNORD3C37.66427553.62E-10lincRNARP11-403B2.652.6627520.007059185lincRNARP11-13N12.10.18782970.026473897lincRNASH3RF3-AS12.794388280.045879799PseudogeneHSPA74.155901880.026473897NAlincRNARP11-13N12.10.057158630.005977715lincRNARP11-300J18.10.064890130.026369459PseudogeneRP11-252O2.280.49832940.000136973BLAAntisenseRP11-543H23.210.82435110.007934374AntisenseRP11-258F1.12.379224520.015332852AntisenseTBL1XR1-AS117.33127720.015532413AntisenseAFAP1-AS13.183253290.017192359AntisenseFAM201A1.763191820.033190051AntisenseRP11-61I13.32.01695690.034644143AntisenseAC137932.64.489700880.046685483lincRNASNORD3C29.15098682.75E-09lincRNARP11-13N12.10.059154640.001230207lincRNARP11-638F5.15.01436030.001568731lincRNAFAM225B2.901511660.006760463lincRNALINC003133.270854570.011320488lincRNARP4-723E3.14.544237350.036184405lincRNARP11-1L9.10.534347890.0436353lincRNARP11-713P17.31.928499230.046685483PseudogeneHSPA77.723532050.000344011PseudogeneRPLP0P23.44012320.003849772PseudogeneRP5-1033K19.217.94034020.00962731PseudogeneKRT16P210.8847350.014255406PseudogeneCTD-2575K13.63.951765130.022758622PseudogeneAC000367.12.02528920.031275117PseudogeneRP11-299H22.57.120022070.039950948CNAAntisenseRP11-543H23.215.26939240.006706822AntisenseRP11-258F1.12.776412860.032959908AntisenseRP5-1185I7.116.55474130.03784948AntisenseRP11-350G8.53.193144750.039819746AntisenseAC004066.30.453105630.040012906AntisenseRP13-126C7.16.535827890.040012906lincRNASNORD3C16.63814732.43E-07lincRNARP11-13N12.10.102660910.009545421PseudogeneHSPA713.92407571.48E-05PseudogeneRPLP0P23.566698030.029432652PseudogeneMTND6P62.059779670.047701809SFC superior frontal cortex, NA nucleus accumbens, BLA basolateral amygdala, CNA central nucleus of the amygdala, FC fold change, FDR false discovery rate, LincRNA long intergenic noncoding RNA.Table 3Functional ontology of long noncoding RNAs (lncRNAs) altered in alcohol use disorder.Biological processNumber of lncRNAsmRNA splicing, via spliceosome11RNA processing10mRNA processing10Nuclear-transcribed mRNA poly(A) tail shortening8Nuclear-transcribed mRNA catabolic process7
