QKI

Description

The QKI (QKI, KH domain containing RNA binding) is a protein-coding gene located on chromosome 6.

Quaking homolog, KH domain RNA binding (mouse), also known as QKI, is a protein which in humans is encoded by the QKI gene. QKI belongs to a family of RNA-binding proteins called STAR proteins for Signal Transduction and Activation of RNA. They have an HNRNPK homology (KH) domain embedded in a 200-amino acid region called the GSG domain. Other members of this family include SAM68 (KHDRBS1) and SF1 . Two more new members are KHDRBS3 and KHDRBS2. The QKI gene is implicated as being important in schizophrenia, and QKI controls translation of many oligodendrocyte-related genes.

QKI is an RNA-binding protein that regulates various RNA metabolic processes including pre-mRNA splicing, circular RNA (circRNA) formation, mRNA export, mRNA stability and translation. It plays a role in several cellular processes, such as mRNA storage into stress granules, apoptosis, lipid deposition, interferon response, glial cell fate and development. QKI specifically binds to the 5'-NACUAAY-N(1,20)-UAAY-3' RNA core sequence and acts as a mRNA modification reader that recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G). QKI promotes the formation of circular RNAs (circRNAs) during the epithelial to mesenchymal transition and in cardiomyocytes by binding to sites flanking circRNA-forming exons. It plays a central role in myelinization through three distinct mechanisms: 1) promoting the stability of target mRNAs such as MBP, SIRT2 and CDKN1B, which promotes oligodendrocyte differentiation, 2) participating in mRNA transport by regulating the nuclear export of MBP mRNA, and 3) indirectly regulating mRNA splicing of MAG pre-mRNA by inhibiting the translation of HNRNPA1 mRNA splicing factor. QKI is also involved in microglia differentiation and remyelination by regulating microexon alternative splicing of the Rho GTPase pathway. It promotes monocyte differentiation by regulating pre-mRNA splicing in naive peripheral blood monocytes and is an important regulator of muscle development, being required for the contractile function of cardiomyocytes by regulating alternative splicing of cardiomyocyte transcripts. QKI acts as a negative regulator of thermogenesis by decreasing stability, nuclear export and translation of mRNAs encoding PPARGC1A and UCP1. It is also required for visceral endoderm function and blood vessel development and may play a role in smooth muscle development. In addition to its RNA-binding activity, QKI acts as a nuclear transcription coactivator for SREBF2/SREBP2, promoting SREBF2/SREBP2-dependent cholesterol biosynthesis, which participates in myelinization and is required for eye lens transparency. QKI also acts as a translational repressor for HNRNPA1 and GLI1. Translation inhibition of HNRNPA1 during oligodendrocyte differentiation prevents inclusion of exon 12 in MAG pre-mRNA splicing. QKI is involved in astrocyte differentiation by regulating translation of target mRNAs. QKI interacts with G3BP1 to localize m7G-containing mRNAs into stress granules in response to stress, thereby suppressing their translation. It acts as a negative regulator of angiogenesis by binding to mRNAs encoding CDH5, NLGN1 and TNFAIP6, promoting their degradation. QKI can also induce apoptosis in the cytoplasm. Heterodimerization with other isoforms results in nuclear translocation of isoform QKI7 and suppression of apoptosis. QKI binds some microRNAs and promotes stabilization of miR-122 by mediating recruitment of poly(A) RNA polymerase TENT2, leading to 3' adenylation and stabilization of miR-122.

QKI is also known as Hqk, QK, QK1, QK3, hqkI.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing