| 1994 |
GRSF1 is a cytoplasmic poly(A)+ mRNA binding protein that interacts with a conserved G-rich RNA element. It contains three RNA recognition motifs and two auxiliary domains, and was localized to the cytoplasm by indirect immunofluorescence. In vivo UV cross-linking demonstrated GRSF1 is bound to poly(A)+ mRNA in living human cells. |
Northwestern screening, immunofluorescence, in vivo UV cross-linking, Western blot |
Nucleic acids research |
Medium |
8036161
|
| 1999 |
GRSF1 specifically binds the 5' UTR of influenza virus NP mRNA and acts as a positive translational regulator. Recombinant GRSF1 stimulated translation of NP 5'UTR-driven templates in cell-free translation systems; depletion of GRSF1 from HeLa extracts reduced translation, which was restored upon reconstitution. |
Yeast three-hybrid system, gel shift assays, cell-free translation assays, HeLa extract depletion/reconstitution |
Proceedings of the National Academy of Sciences of the United States of America |
High |
10359774
|
| 2002 |
The RNA binding activity of GRSF1 maps to RRM2 (amino acids 194–275), and the GRSF1 RNA binding site on influenza NP and NS1 5'UTRs is the sequence AGGGU. Deletion of the Ala-rich region in addition to RRM1 increased translational activation ~4-fold over wild-type. GRSF1 functions by selectively recruiting cellular and viral mRNAs containing 5'UTR GRSF1 binding sites to polyribosomes via interactions with cellular proteins. |
GST-GRSF1 deletion mutants, in vitro translation assays, polysome fractionation, cDNA microarray |
Journal of virology |
High |
12239318
|
| 2013 |
A mitochondrial isoform of GRSF1 accumulates in discrete foci (mitochondrial RNA granules) in the mitochondrial matrix, where it interacts with RNase P and is required for processing of both classical and tRNA-less RNA precursors. Loss of GRSF1 causes abnormal cleavage of primary RNA transcripts, decreased expression of mitochondrially encoded proteins, and mitochondrial dysfunction. |
Immunofluorescence/subcellular fractionation, Co-immunoprecipitation (GRSF1–RNase P), RNA processing assays in GRSF1-depleted cells |
Cell metabolism |
High |
23473034
|
| 2014 |
GRSF1 promotes translation of the SNARE protein Use1 by binding to G-repeats in the alternatively spliced 5'UTR of Use1 mRNA, and this is required for expansion of erythroblasts. Knockdown of either Grsf1 or Use1 abrogated erythroblast expansion. |
RNA band shift assays, reporter translation assays, siRNA knockdown, erythroblast expansion assays |
PloS one |
Medium |
25184340
|
| 2015 |
GRSF1 mediates miR-346-dependent upregulation of hTERT by binding to the miR-346 middle sequence motif (CCGCAU) in the 'bulge loop' formed when miR-346 is bound to the hTERT 3'UTR, facilitating ribosome recruitment in an AGO2-independent manner. Replacement of miR-138's middle sequence with that of miR-346 switches the outcome to GRSF1-dependent upregulation. |
RNA immunoprecipitation, reporter assays, ribosome recruitment assays, miRNA sequence swap experiments |
Scientific reports |
Medium |
26507454
|
| 2016 |
GRSF1 binds the nuclear DNA-encoded lncRNA RMRP after its import into mitochondria and increases RMRP abundance in the matrix. Loss of GRSF1 lowers mitochondrial RMRP levels, suppresses oxygen consumption rates, and modestly reduces mitochondrial DNA replication priming. |
Affinity RNA pull-down followed by mass spectrometry, RIP, siRNA knockdown, oxygen consumption measurement |
Genes & development |
High |
27198227
|
| 2017 |
GRSF1 requires the simultaneous presence of all three qRRM (quasi-RNA recognition motif) domains for high-affinity RNA binding (KD ~0.5 µM for full-length protein). Deletion of any single qRRM impairs binding; deletion of the acidic auxiliary domain improves binding, suggesting a regulatory role; deletion of the Ala-rich domain does not affect RNA binding. Isolated individual qRRM domains have negligible RNA-binding affinity. |
Recombinant protein expression, quantitative RNA electrophoretic mobility shift assays (EMSA) with truncation mutants |
Biochimica et biophysica acta. General subjects |
High |
29288125
|
| 2018 |
GRSF1 loss impairs mitochondrial respiration (respiratory complexes I and IV) and increases ROS, leading to DNA damage, growth suppression, and a senescent phenotype with elevated IL6. Mechanistically, mTOR is activated downstream of oxidative stress, which activates NF-κB to induce IL6 gene transcription and a pro-inflammatory program. |
GRSF1 siRNA knockdown, respiratory complex assays, ROS measurement, immunoblotting, NF-κB/mTOR pathway analysis |
Nucleic acids research |
Medium |
30753671
|
| 2018 |
GRSF1 levels decline in senescent cells through reduced protein stability (not at mRNA level). Lowering GRSF1 causes mitochondrial stress, elevated superoxide, increased DNA damage, diminished proliferation, increased SA-β-gal activity, and elevated IL6 production/secretion. |
Protein stability assays, GRSF1 knockdown, ROS measurement, SA-β-gal assay, IL6 ELISA |
Aging |
Medium |
30086537
|
| 2018 |
GRSF1 together with the mitochondrial degradosome (SUV3-PNPase complex) restricts mitochondrial antisense RNA (including G-quadruplex-forming species). GRSF1 acts as a G-quadruplex-melting co-factor enabling degradation of antisense mtRNAs by the SUV3-PNPase complex. |
Genetic/biochemical characterization of antisense mtRNA levels upon depletion of complex components |
Molecular & cellular oncology |
Medium |
30525095
|
| 2019 |
GRSF1 inhibits myoblast differentiation by directly targeting mitochondrial GPX4 mRNA, promoting GPX4 expression which reduces ROS levels; reduction in mitochondrial ROS is necessary for myogenic differentiation. Loss of GRSF1 promotes differentiation by reducing GPX4 and increasing ROS. |
siRNA knockdown, ROS measurement, myogenic differentiation assays in vitro and in vivo |
Experimental cell research |
Medium |
31085189
|
| 2021 |
GRSF1 directly binds GUUU motifs within the 3'UTR of YY1 mRNA (region 2663-2847) to enhance YY1 mRNA stability. YY1 in turn feeds back to promote GRSF1 expression by binding the GRSF1 promoter. GRSF1 and miR-30e-5p competitively regulate YY1 by binding the same 3'UTR region. |
RNA immunoprecipitation, luciferase reporter assays, RNA pull-down, ChIP assay, shRNA knockdown |
Journal of experimental & clinical cancer research : CR |
Medium |
34998399
|
| 2022 |
GRSF1 directly upregulates GPX4 at the translational level in cardiomyocytes. Knockdown of GRSF1 increased sensitivity to ferroptosis and impaired the cardioprotective effect of geniposide in oxidative-stressed cardiomyocytes. |
siRNA knockdown, translation assays, ferroptosis assays, in vivo myocardial infarction model |
Frontiers in pharmacology |
Medium |
35600863
|
| 2022 |
Host adaptive mutations in the 2009 pH1N1 PA gene enhance cytosolic accumulation and translation efficiency of viral mRNAs via GRSF1. Mutations to the GRSF1 binding site in viral NP mRNA 5'UTR, as well as GRSF1 knockdown, reduced cytosolic mRNA accumulation and translation efficiency. |
Quantitative translation/transcription assays, GRSF1 knockdown, GRSF1 binding site mutagenesis |
Communications biology |
Medium |
36253464
|
| 2023 |
GRSF1 directly interacts with G-tracts in the coding region (CDS) of FGA, FGB, and FGG mRNAs via its qRRM2 domain and decreases their stability, thereby reducing fibrinogen expression and attenuating hypercoagulability. Overexpression of GRSF1 in old mice liver decreased plasma fibrinogen and reduced hypercoagulability; knockdown in young mice increased fibrinogen and promoted coagulation. |
RNA immunoprecipitation, RNA pull-down, domain deletion mutants, in vivo overexpression/knockdown mouse liver models, coagulation assays |
Cell death & disease |
High |
37923734
|
| 2024 |
GRSF1 is important for nuclear export of influenza A virus NP mRNAs as well as their translation. Mutation of the GRSF1 binding site in the NP mRNA 5'UTR reduced NP protein production, cytosolic accumulation of NP mRNA, and attenuated viral growth in mammalian cells. |
Recombinant virus rescue with GRSF1 binding site mutation, NP protein/mRNA quantification, in vitro mRNA translation assay |
Viruses |
Medium |
39066299
|
| 2024 |
GRSF1 interacts with SOD2 mRNA in granulosa cells (demonstrated by RNA immunoprecipitation), and knockdown of SOD2 reverses the protective effects of GRSF1 overexpression on mitochondrial function, indicating GRSF1 modulates oxidative stress through regulating SOD2. |
RNA immunoprecipitation, siRNA knockdown, mitochondrial function assays |
Reproduction (Cambridge, England) |
Low |
38819377
|
| 2025 |
GRSF1 promotes translation of COX1 mRNA in mitochondria. miR-19-3p suppresses GRSF1 expression; loss of GRSF1 reduces COX1 protein levels, impairs mitochondrial function, and aggravates neuronal injury after subarachnoid haemorrhage. |
Lentiviral overexpression/knockdown in neurons and rat SAH model, miR-19-3p mimic/inhibitor, COX1 protein quantification |
Stroke and vascular neurology |
Medium |
39266212
|
| 2026 |
GRSF1 maintains cardiac BCAA homeostasis by directly binding G-tracts in the coding region of BCKDHB mRNA through its qRRM domain, promoting BCKDHB mRNA stability and increasing BCKDHB protein expression. Cardiomyocyte-specific GRSF1 deletion led to dilated cardiomyopathy and heart failure; overexpression attenuated pressure-overload heart failure. Functional recovery by GRSF1 overexpression was blocked by cardiac-specific BCKDHB deletion, establishing epistasis. |
Cardiomyocyte-specific conditional KO and overexpression mice, metabolomics, GRSF1 qRRM mutant mice, BCKDHB cardiac-specific KO epistasis, mRNA stability assays |
Circulation |
High |
41487100
|
| 2026 |
LINC00942 interacts with GRSF1 and facilitates binding of GRSF1 to complex I mRNA in mitochondria, enhancing translation efficiency of complex I subunits, increasing complex I protein levels and mitochondrial oxidative phosphorylation activity, while suppressing ferroptosis in hepatocellular carcinoma cells. |
RNA pull-down with mass spectrometry (GRSF1 interaction), RIP, complex I activity assays, ferroptosis assays |
Science China. Life sciences |
Medium |
41530642
|
| 2025 |
Super-resolution STED nanoscopy (smFISH-STED) revealed spatial relationships between distinct mitochondrial mRNA species and GRSF1 as an RNA granule marker protein, demonstrating adaptive changes in mRNA distribution and quantity in challenged mammalian cells. |
smFISH combined with STED and MINFLUX super-resolution microscopy |
bioRxivpreprint |
Medium |
bio_10.1101_2025.01.23.634455
|