DGCR8-dependent efficient pri-miRNA processing of human pri-miR-9-2
| Autor: | Yoshika Hayakawa-Yano, Masahiro Nogami, Atsushi Nakanishi, Kazumasa Miyamoto, Hideyuki Okano, Masato Yano |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
and fluorescence DGCR8 Haploinsufficiency DRE DGCR8-responsive RNA element Biochemistry DGCR8 DiGeorge syndrome critical region gene 8 Cell Line Microprocessor complex 03 medical and health sciences DGCR8 Gene pri-miR-9-2 Cell Line Tumor microRNA Humans RNA Processing Post-Transcriptional Molecular Biology Gene DiGeorge syndrome Drosha miRNA 030102 biochemistry & molecular biology biology RNA RNA-Binding Proteins Cell Biology Cell biology schizophrenia MicroRNAs neurogenesis CLIP UV-cross-linking and immunoprecipitation 030104 developmental biology pri-miRNA primary transcripts of microRNA biology.protein poly(A) polyadenylation ribonuclease pri-miRNA processing Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | 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 ratiometric 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|