DGCR8
Description
The DGCR8 (DGCR8 microprocessor complex subunit) is a protein-coding gene located on chromosome 22.
DGCR8 (DiGeorge syndrome critical region 8) is a protein crucial for microRNA (miRNA) processing. It is a component of the microprocessor complex, working alongside Drosha, an RNase III enzyme. Together, they cleave a primary transcript known as pri-miRNA, producing a characteristic stem-loop structure called pre-miRNA. Pre-miRNA is then further processed by Dicer to generate miRNA fragments. DGCR8 contains an RNA-binding domain and is believed to bind pri-miRNA to stabilize it for Drosha processing. DGCR8 also contributes to DNA repair. Specifically, the removal of UV-induced DNA photoproducts during transcription-coupled nucleotide excision repair (TC-NER) depends on JNK phosphorylation of DGCR8 on serine 153. This DNA repair function is independent of DGCR8's role in miRNA biogenesis. DGCR8 also participates in repairing oxidative DNA damage caused by hydrogen peroxide (H2O2). Cells depleted of DGCR8 are sensitive to H2O2.
DGCR8 is a key component of the microprocessor complex, a protein complex essential for the initial step of microRNA (miRNA) biogenesis. It acts as a RNA- and heme-binding protein, playing a crucial role in processing primary miRNA transcripts (pri-miRNAs) into precursor miRNAs (pre-miRNAs) within the nucleus. DGCR8 acts as a molecular anchor, recognizing pri-miRNAs at the dsRNA-ssRNA junction and directing DROSHA, another component of the complex, to cleave 11 base pairs away from the junction. This cleavage releases hairpin-shaped pre-miRNAs, which are subsequently processed by the cytoplasmic DICER to produce mature miRNAs. The binding of DGCR8 to pri-miRNAs is influenced by heme: Heme-bound DGCR8 dimers form cooperative trimers and actively trigger pri-miRNA cleavage, while heme-free DGCR8 monomers bind as dimers with significantly reduced activity. Both double-stranded and single-stranded regions of a pri-miRNA are required for DGCR8 binding. DGCR8 specifically recognizes and binds to N6-methyladenosine (m6A)-containing pri-miRNAs, a modification essential for their processing. DGCR8 is also involved in silencing embryonic stem cell self-renewal.
DGCR8 is also known as C22orf12, DGCRK6, Gy1, pasha.
