DGCR8-dependent efficient pri-miRNA processing of human pri-miR-9-2

Microprocessor complex, including DiGeorge syndrome critical region gene 8 (DGCR8) and DROSHA, recognizes and cleaves primary transcripts of microRNAs (pri-miRNAs) in the maturation of canonical miRNAs. The study of DGCR8 haploinsufficiency reveals that the efficiency of this activity varies for different miRNA species. It is thought that this variation might be associated with the risk of schizophrenia with 22q11 deletion syndrome caused by disruption of the DGCR8 gene. However, the underlying mechanism for varying action of DGCR8 with each miRNA remains largely unknown. Here, we used in vivo monitoring to measure the efficiency of DGCR8-dependent microprocessor activity in cultured cells. We confirmed that this system recapitulates the microprocessor activity of endogenous pri-miRNA with expression of a ratio-metric fluorescence reporter. Using this system, we detected mir-9-2 as one of the most efficient targets. We also identified a novel DGCR8-responsive RNA element, which is highly conserved among mammalian species and could be regulated at the epi-transcriptome (RNA modification) level. This unique feature between DGCR8 and pri-miR-9-2 processing may suggest a link to the risk of schizophrenia.

Automated summary

The study explores the varying efficiency of DGCR8 in processing different miRNA species, potentially related to the risk of schizophrenia in 22q11 deletion syndrome. In vivo monitoring reveals mir-9-2 as one of the most efficient targets of DGCR8-dependent microprocessor activity in cultured cells. A novel DGCR8-responsive RNA element, highly conserved among mammalian species, may play a role in regulating pri-miR-9-2 processing and potentially linking to schizophrenia risk.