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G-RICH RNA SEQUENCE-BINDING FACTOR 1; GRSF1

G-RICH RNA SEQUENCE-BINDING FACTOR 1; GRSF1

HGNC Approved Gene Symbol: GRSF1Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38): 4:70,815,782-70,843,273 (from NCBI)▼ Cloning and ExpressionNuclear...

HGNC Approved Gene Symbol: GRSF1

Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38): 4:70,815,782-70,843,273 (from NCBI)

▼ Cloning and Expression
Nuclear posttranscriptional events, such as pre-mRNA splicing, RNA stability, and mRNA transport and translation, are influenced by RNA-protein interactions. Qian and Wilusz (1991) found that the RNA-binding site of the cellular 50-kD DSEF1 protein consists of a 14-base G-rich element. Using a Northwestern strategy to screen a HeLa cell cDNA library with the G-rich RNA element as a probe, Qian and Wilusz (1994) obtained a full-length cDNA clone, designated G-rich RNA sequence-binding factor-1 (GRSF1), encoding a cellular protein that binds RNAs containing the G-rich element. The GRSF1 cDNA has a long 3-prime untranslated region containing 2 polyadenylation signals. The open reading frame encodes a deduced 424-amino acid protein with a calculated molecular mass of 48 kD. The protein contains 3 RNA recognition motifs and 2 auxiliary domains. Northern blot analysis indicated 2 predominant mRNAs of 1.7 and 2.8 kb. Indirect immunofluorescence microscopy with anti-GRSF1 monoclonal antibody and in vivo UV crosslinking experiments suggested that GRSF1 is a cytosolic poly(A)+ mRNA-binding protein.

▼ Gene Function
By yeast 3-hybrid screening of a mouse testis cDNA library, followed by RNA mobility gel shift assays, Ufer et al. (2008) found that Grsf1 bound an AGGGGA motif in the 5-prime UTR of mitochondrial glutathione peroxidase-4 (GPX4; 138322). Grsf1 upregulated Gpx4 UTR-dependent reporter gene expression, recruited mitochondrial Gpx4 mRNA to translationally active polysomes, and coimmunoprecipitated with Gpx4 mRNA. During embryonic mouse brain development, Grsf1 and mitochondrial Gpx4 were coexpressed, and knockdown of Grsf1 via small interfering RNA prevented embryonic Gpx4 expression. Compared with mock controls, Grsf1-knockdown embryos showed developmental retardation that paralleled increased apoptosis and massive lipid peroxidation. Overexpression of mitochondrial Gpx4 prevented the apoptotic changes and rescued development in Grsf1-knockdown embryos. Ufer et al. (2008) concluded that GRSF1 upregulates translation of GPX4 mRNA and that both proteins are required for embryonic brain development.

▼ Mapping
By fluorescence in situ hybridization, Banga et al. (1996) mapped the GRSF1 gene to chromosome 4q13.

Tags: 4q13.3