[대학원 생명과학과 세미나 안내]
연사 : 우재성 교수(고려대학교 생명과학부)
연제 : Structural insights into primary microRNA processing
일시 : 2017년 9월 1일 (금) 오후 5시
장소 : 하나과학관 A동 B131호
초청교수 : 최의주 교수
Abstract
MicroRNAs (miRNAs) are small noncoding RNA molecules that control the expression of their target mRNAs. In the initial step of miRNA maturation, primary miRNA transcripts (pri-miRNAs) are prcessed by the Microprocessor complex, whose fidelity is critical for generation of functional miRNAs. For accurate processing of pri-miRNAs, Microprocessor comprehensively recognizes several structural features and sequence motifs of pri-miRNAs, which has been discovered by previous bioinformatical and biochemical studies. To understand the molecular mechanism of pri-miRNA recognition and processing, we reconstitute human Microprocessor with purified recombinant proteins. We find the ruler function of DROSHA and specify the accessary roles of DGCR8 domains by in vitro processing assays. Furthermore, we solve the atomic structure of DROSHA in complex with the C-terminal helix of DGCR8. The overall structure of DROSHA is unexpectedly similar to that of DICER, suggesting that DROSHA may have evolved from an ancestral DICER. DROSHA however exhibits several unique features, such as a kinked conformation and two long DROSHA-specific insertions, which together contribute to substrate recognition and processing. In addition, we identify two DGCR8 binding sites on DROSHA which provide key information to build the heterotrimeric Microprocessor model. These findings clarify long standing controversies over the Microprocessing mechanism and allow us to build a general model for pri-miRNA processing.