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Chunk #20 — Results — Expression of splicing factors in AUD

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Alcohol use disorder causes global changes in splicing in the human brain.
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that examination of the RNA profiles from the whole brain may be inaccurate due to region-specific transcriptomic alterations and that the RNA profiling in the brain should rather be done in a region-specific or/and lineage-specific manner. Next, we interrogated RNA sequencing datasets from the human study by aligning the list 127 spliceosomal genes with the list of genes differentially expressed in patients with AUD. Only one of the splicing factors, heat shock protein family A (Hsp70) member 6 (HSPA6), was detected in both lists, and its expression was consistently and markedly elevated in all brain regions. Thus, in SFC, HSPA6 mRNA levels were 19.7-fold increased. In NA, HSPA6 mRNA was approximately twofold upregulated, but this difference did not reach statistical significance. In BLA, HSPA6 mRNA concentrations were 14.8-fold increased. Finally, in the CNA, the greatest increase in HSPA6 mRNA was detected, 22.4-fold (P < 0.05, Fig. 4). Next, we checked if alcohol has a concerted effect on the spliceosomal proteome. Total expression of 127 spliceosomal genes was analyzed by averaging the expression of all individual genes, with mRNA levels of each gene in the control group assigned a value of 1, and expression of the same gene in the AUD