DiGeorge syndrome critical region 8; microprocessor complex subunit DGCR8 (DGCR8, C22orf12, DGCRK6, LP4941)
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Function
- component of the microprocessor complex that acts as a RNA- & heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis
- component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus
- within the microprocessor complex, DGCR8 functions as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction & directs DROSHA to cleave 11 bp away from the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs
- heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) & is active in triggering pri-miRNA cleavage
- heme-free DGCR8 monomer binds pri-miRNAs as a dimer & is much less active
- both double-stranded & single-stranded regions of a pri-miRNA are required for its binding
- involved in silencing of embryonic stem cells self-renewal
- monomer; in absence of heme
- homodimer; the associationwith heme promotes its dimerization
- interacts with ILF3, NCL & DROSHA
- binds 1 heme group per homodimer
Structure
- both DRBM domains are required for efficient binding to pri-miRNA
- the region between residues 276 & 498 has an autoinhibitory function on pri-miRNA processing activity
- contains 2 DRBM (double-stranded RNA-binding) domains
- contains 1 WW domain
Compartment
- nucleus. nucleus, nucleolus
- colocalizes with nucleolin & DROSHA in the nucleolus
- mostly detected in the nucleolus as electron-dense granular patches around the fibrillar center & granular component
- also detected in the nucleoplasm as small foci adjacent to splicing speckles near the chromatin structure
- localized with DROSHA in P-bodies
Alternative splicing
named isoforms=3
Expression
ubiquitously expressed