| 1993 |
SF2/ASF has two functional domains: an N-terminal RNA recognition motif (RRM) with specific protein-RNA contacts (Phe56 and Phe58 in RNP-1 submotif essential for constitutive splicing) and a C-terminal RS domain required for constitutive splicing; the two RRMs act synergistically for RNA binding, while alternative splicing activity does not require the RS domain. |
In vitro splicing assays with site-directed mutagenesis of RRM and RS domain; RNA binding assays with recombinant mutant proteins |
The EMBO journal |
High |
8223480
|
| 1993 |
ASF/SF2 contains two diverged RBDs both essential for constitutive splicing activity; the RS domain is required for essential splicing but not for splice site switching; deletion isoforms lacking either domain act as dominant-negative splicing repressors. |
In vitro splicing assays with deletion and substitution mutants of ASF/SF2 |
The EMBO journal |
High |
8223481
|
| 1993 |
SF2/ASF enhances downstream 5' splice site use by increasing the strength of U1 snRNP binding indiscriminately to all sites, as shown by ribonuclease H protection experiments. |
Ribonuclease H protection assay; U1 snRNP cleavage and site mutation experiments |
The EMBO journal |
High |
8253084
|
| 1994 |
ASF/SF2 can specifically recognize pre-mRNA 5' splice sites in a sequence-specific manner; point mutations in the 5' splice site consensus reduce binding up to 100-fold. |
UV crosslinking and gel shift assays with purified recombinant ASF/SF2 and mutant pre-mRNAs |
Proceedings of the National Academy of Sciences of the United States of America |
High |
7512732
|
| 1995 |
ASF/SF2 forms a ternary complex with U1 snRNP and pre-mRNA dependent on a functional 5' splice site; complex formation requires one functional RNA binding domain and the RS domain of ASF/SF2, and the U1-C protein of U1 snRNP. |
Reconstituted ternary complex assembly with purified components; domain deletion analysis |
Nucleic acids research |
High |
7667103
|
| 1997 |
Both phosphorylation and dephosphorylation of ASF/SF2 are required for pre-mRNA splicing in vitro: phosphorylated ASF/SF2 promotes spliceosome assembly, while dephosphorylation is required for the first transesterification reaction; thiophosphorylated ASF/SF2 (resistant to dephosphorylation) blocks the first catalytic step. |
In vitro splicing assays with phosphorylated, unphosphorylated, and thiophosphorylated ASF/SF2 in SR-depleted HeLa extracts |
RNA (New York, N.Y.) |
High |
9404896
|
| 1998 |
Phosphorylation of the RS domain of ASF/SF2 differentially affects its protein-protein interactions: it positively affects interaction with U1 snRNP 70K, and differentially (positively, negatively, or not at all) regulates interactions with other splicing factors; phosphorylation is required for constitutive splicing but not for splicing activation. |
Co-immunoprecipitation and interaction assays comparing phosphorylated vs. unphosphorylated ASF/SF2 |
The EMBO journal |
High |
9799243
|
| 1998 |
cdc2 kinase (cdc2-cyclin B complex) phosphorylates the RS domain of SF2/ASF specifically at serines 227, 238, and 199, suggesting cell-cycle-dependent regulation of splicing. |
In vitro kinase assay with recombinant cdc2 kinase and mutant SF2/ASF proteins; phosphopeptide mapping |
Biochemical and biophysical research communications |
Medium |
9731229
|
| 1999 |
SRPK1 and SRPK2 physically bind to and phosphorylate SF2/ASF; binding maps to an (Arg-Ser)8 repeat region beginning at residue 204; SRPKs bind unphosphorylated but not phosphorylated SF2/ASF; expression of kinase-inactive SRPK2 causes cytoplasmic accumulation of SF2/ASF, establishing that SRPK-mediated phosphorylation regulates SF2/ASF nuclear localization. |
GST-SF2/ASF affinity chromatography from HeLa cells; recombinant SRPK1/2 in vitro kinase and binding assays; co-IP in COS7 cells; far-Western analysis; dominant-negative SRPK2 expression with localization imaging |
The Journal of biological chemistry |
High |
10196197
|
| 2001 |
SF2/ASF binds to an exonic splicing enhancer (ESE3) in HIV-1 tat exon and stimulates U2AF65 binding to a suboptimal polypyrimidine tract in an ESE3-dependent manner; this activity does not require the RS domain, demonstrating an RS-domain-independent mechanism for U2AF recruitment. |
In vitro splicing assays; U2AF65 binding assay; deletion mutants of SF2/ASF lacking RS domain |
Journal of molecular biology |
High |
11575921
|
| 2002 |
The second RNA binding domain (RBD2) of ASF/SF2 is both necessary and sufficient for splicing repressor function; the SWQDLKD motif within RBD2 is essential for splicing repression but not for RNA binding; repressor activity is position-dependent (intronic but not exonic). |
MS2-ASF/SF2 fusion protein tethering assay; domain deletion and substitution mutagenesis; in vitro splicing |
The Journal of biological chemistry |
High |
11801589
|
| 2004 |
Hypophosphorylated ASF/SF2 preferentially binds the mRNA export receptor TAP; overexpression of ASF/SF2 relocalizes TAP to nuclear speckles; ASF/SF2 in mature mRNP is hypophosphorylated while nucleoplasmic ASF/SF2 is hyperphosphorylated, indicating dephosphorylation promotes incorporation into mRNPs and TAP recruitment for mRNA export. |
Immunoprecipitation with phospho-specific conditions; subnuclear fractionation; nuclear speckle co-localization imaging |
The Journal of biological chemistry |
High |
15184380
|
| 2004 |
SF2/ASF recruitment to nuclear stress bodies (nSBs) upon heat shock is mediated by its second RNA recognition motif (RRM2); mutations in the first alpha-helix of RRM2 abrogate association with nSBs and disrupt alternative splicing activity in vivo; SF2/ASF binds satellite III transcripts via RRM2. |
Mutagenesis of RRM2 with immunofluorescence localization; in vivo alternative splicing assay; gel mobility shift assay with RRM2 domain |
Nucleic acids research |
High |
15302913
|
| 2005 |
Depletion of ASF/SF2 in vivo causes DNA double-strand breaks and R-loop formation (RNA:DNA hybrids) on the non-template strand of transcribed genes; ASF/SF2 prevents R-loop formation in a reconstituted in vitro transcription system; stable RNase H overexpression suppresses the DNA fragmentation and hypermutation phenotypes. |
siRNA depletion with comet assay and DNA fragmentation analysis; in vitro transcription reconstitution; RNase H overexpression rescue |
Cell |
High |
16096057
|
| 2005 |
SF2/ASF controls alternative splicing of Ron proto-oncogene by binding a purine-rich exonic splicing enhancer in exon 12, promoting skipping of exon 11 to produce the constitutively active DeltaRon isoform; this drives epithelial-to-mesenchymal transition and cell motility. |
Overexpression and RNAi experiments; minigene splicing assays; cell motility assays; DeltaRon-specific knockdown rescue |
Molecular cell |
High |
16364913
|
| 2007 |
SF2/ASF is a proto-oncogene that transforms immortal rodent fibroblasts; it controls alternative splicing of BIN1 (removing tumor suppressor activity), MNK2 (producing a MAP kinase-independent eIF4E kinase isoform), and S6K1 (producing an oncogenic isoform); knockdown of either SF2/ASF or S6K1 isoform-2 reverses transformation. |
Overexpression transformation assays; nude mouse xenograft; alternative splicing minigene analysis; shRNA knockdown |
Nature structural & molecular biology |
High |
17310252
|
| 2007 |
SRPK1 phosphorylates ASF/SF2 RS domain in a directional, processive manner from C-terminus to N-terminus (RS1 region), using a 'grab-and-pull' mechanism; initiation requires a docking groove near the C-terminus of RS1 and proceeds N-terminally. |
Region-specific phosphorylation monitoring via engineered protease cleavage sites; Arg-to-Lys and Ser-to-Ala mutations; in vitro kinase assays with single-turnover analysis |
Journal of molecular biology |
High |
18155240
|
| 2008 |
SF2/ASF promotes translation initiation of bound mRNAs by suppressing 4E-BP activity through interactions with both mTOR and phosphatase PP2A, functioning as an adaptor to regulate cap-dependent translation of specific mRNAs; this requires eIF4E. |
In vivo translation assays; co-immunoprecipitation of SF2/ASF with mTOR and PP2A; 4E-BP phosphorylation assays |
Molecular cell |
High |
18439897
|
| 2008 |
SF2/ASF activates the mTORC1 branch of the mTOR signaling pathway (measured by S6K and eIF4EBP1 phosphorylation), bypassing upstream PI3K/Akt signaling; mTORC1 activation is essential for SF2/ASF-mediated transformation, as rapamycin blocks transformation in vitro and in vivo. |
S6K/eIF4EBP1 phosphorylation assays; rapamycin treatment; shRNA knockdown of mTOR, Raptor, Rictor; in vitro transformation and nude mouse tumor assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
18832178
|
| 2008 |
SRPK1 uses adaptable molecular interactions including an electropositive pocket stabilizing newly phosphorylated serines to facilitate processive phosphorylation of ASF/SF2; the RRM1-RRM2 module fine-tunes processivity during later phases of phosphorylation. |
Single-turnover and multiturnover kinetic methods; deletion studies; mutational analysis of SRPK1-SF2/ASF interface |
Journal of molecular biology |
High |
18687337
|
| 2009 |
SRPK1 initiates phosphorylation of ASF/SF2 in an 'initiation box' at the C-terminal end of the RS1 segment (middle of RS domain) and proceeds N-terminally; this requires both a docking groove in SRPK1's large lobe and RRM2 on the N-terminal flank of the RS domain. |
Engineered footprinting; single-turnover kinetic experiments; Arg-to-Lys and deletion mutations |
Journal of molecular biology |
High |
19477182
|
| 2010 |
SF2/ASF negatively autoregulates its own expression through multiple post-transcriptional mechanisms: unproductive alternative splicing generating NMD-targeted isoforms, and primarily translational repression via the ultraconserved 3'UTR mediated by RRM2; overexpression shifts target mRNA to monoribosomes. |
Alternative splicing isoform characterization; reporter assays with 3'UTR constructs; polyribosome fractionation; Dicer-independent translation repression analysis |
Nature structural & molecular biology |
High |
20139984
|
| 2010 |
Sam68 promotes AS-NMD (alternative splicing coupled nonsense-mediated decay) of SF2/ASF transcripts, reducing SF2/ASF protein levels during EMT; Sam68 phosphorylation by ERK1/2 signaling controls this regulation. |
Overexpression and siRNA knockdown of Sam68; RT-PCR analysis of SF2/ASF splice variants; ERK1/2 inhibition; phosphorylation assays |
The Journal of cell biology |
High |
20876280
|
| 2010 |
SF2/ASF promotes pri-miR-7 maturation by directly interacting with the primary transcript to facilitate Drosha cleavage, independently of SF2/ASF's splicing function; mature miR-7 in turn targets SF2/ASF 3'UTR to repress its translation, forming a negative feedback loop. |
miRNA deep sequencing; RNA immunoprecipitation; Drosha cleavage assay; reporter assays for miR-7 targeting; splicing-deficient SF2/ASF mutant analysis |
Molecular cell |
High |
20385090
|
| 2010 |
Arginine methylation at R93, R97, and R109 of SF2/ASF (by PRMT) controls its subcellular localization; mutations blocking methylation and positive charge cause cytoplasmic accumulation, reducing nuclear alternative splicing activity, increasing translation stimulation, and abrogating NMD enhancement. |
Site-directed mutagenesis of methylation sites; subcellular fractionation; localization imaging; alternative splicing assays; translation and NMD reporter assays |
Molecular and cellular biology |
High |
20308322
|
| 2010 |
Akt phosphorylates SRSF1 (SRp30a) at serines 199, 201, 227, and 234 to mediate exclusion of Caspase-9 exon 3,4,5,6 cassette; PI3K/Akt pathway inhibition dramatically increases the Casp9a/9b ratio in NSCLC cells. |
Site-directed mutagenesis of SRSF1 phosphorylation sites; PI3K/Akt inhibitor treatment; minigene splicing assays |
Cancer research |
High |
21045158
|
| 2011 |
IL-17 signaling stabilizes CXCL1 mRNA through a pathway involving Act1-TRAF2/TRAF5-SF2/ASF complex formation; SF2/ASF normally binds chemokine mRNA and shortens its half-life, but IL-17 stimulation dissociates SF2/ASF from mRNA, prolonging stability. |
mRNA stability assays; co-immunoprecipitation of TRAF5-TRAF2-Act1-SF2/ASF complex; SF2/ASF overexpression and siRNA depletion; RNA-IP |
Nature immunology |
High |
21822258
|
| 2011 |
SRSF1 phosphorylation is modulated by replicational stress via ATM kinase; hyperphosphorylation of SRSF1 in DNA ligase I-deficient cells (which have chronic DNA damage) alters its subnuclear distribution and shifts alternative splicing patterns of target genes. |
2D phosphoproteomic analysis; ATM inhibition with caffeine; immunofluorescence localization; RT-PCR of alternative splicing targets |
Nucleic acids research |
Medium |
21984412
|
| 2012 |
SRSF1 overexpression transforms mammary epithelial cells requiring the first RRM and nuclear functions; SRSF1 promotes alternative splicing of BIM and BIN1 to produce isoforms lacking pro-apoptotic functions; SRSF1 cooperates with MYC to transform cells partly by potentiating eIF4E activation. |
3D mammary acinar culture; orthotopic transplantation; alternative splicing analysis; eIF4E/MYC cooperation assays; RRM domain mutant analysis |
Nature structural & molecular biology |
High |
22245967
|
| 2012 |
SRSF1 is a direct transcriptional target of MYC; MYC activates SRSF1 transcription through two non-canonical E-boxes in the SRSF1 promoter; increased SRSF1 protein mediates alternative splicing of MKNK2 and TEAD1; SRSF1 knockdown reduces MYC's oncogenic activity. |
ChIP assay showing MYC binding to SRSF1 promoter; promoter reporter assays; MYC knockdown with SRSF1 expression measurement; alternative splicing analysis |
Cell reports |
High |
22545246
|
| 2013 |
SRSF1 and SRSF9 promote β-catenin accumulation by recruiting β-catenin mRNA and enhancing its translation in an mTOR-dependent manner, contributing to Wnt signaling-mediated tumorigenesis. |
mRNA-protein co-immunoprecipitation; translation assays; mTOR inhibition; overexpression studies |
EMBO molecular medicine |
Medium |
23592547
|
| 2013 |
SF2/ASF is recruited to the IL-2 promoter independently of TCR/CD3 signaling, increases IL-2 transcriptional activity, and enhances IL-2 production in SLE T cells; SF2/ASF also limits production of an unstable CD3ζ splice variant to enhance CD3ζ expression. |
Chromatin immunoprecipitation of SF2/ASF at IL-2 promoter; overexpression with IL-2 promoter reporter; RT-PCR of CD3ζ isoforms |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
23319613
|
| 2014 |
SRSF1 binds to a regulatory element in CD6 intron 4 and activates exon 5 splicing; T cell activation causes SRSF1 downregulation, leading to decreased SRSF1 recruitment to CD6 transcript (shown by RNA-IP), combined with increased transcription rate, resulting in exon 5 skipping. |
RNA immunoprecipitation; chromatin immunoprecipitation; histone deacetylase inhibitor treatment; minigene and overexpression experiments |
Journal of immunology |
High |
24890719
|
| 2014 |
SRSF1 inhibits HIV-1 Tat transactivation by competing for overlapping binding sequences within TAR RNA; SRSF1 can also increase basal viral transcription in the absence of Tat by recruiting P-TEFb to TAR from the 7SK snRNP. |
RNA binding competition assays; Tat transactivation reporter assays; P-TEFb co-immunoprecipitation |
Nucleic acids research |
Medium |
25416801
|
| 2017 |
SRSF1 regulates DBF4B pre-mRNA splicing by binding and promoting inclusion of exon 6; the exon 6-containing isoform (DBF4B-FL) is required for cancer cell proliferation and genomic stability maintenance; DBF4B-FL overexpression rescues DNA damage induced by SRSF1 knockdown. |
RNA-IP; siRNA knockdown with DNA damage assays; rescue overexpression; tumor growth assays in mice |
Cell reports |
High |
29262322
|
| 2017 |
SRSF1 promotes VSMC proliferation through a Δ133p53/EGR1/KLF5 pathway: SRSF1 favors induction of the truncated p53 isoform Δ133p53, which transcriptionally activates KLF5 via the Δ133p53-EGR1 complex, accelerating cell-cycle progression. |
Conditional SMC-specific Srsf1 knockout mice with wire injury model; overexpression in rat arteries; siRNA knockdown in human VSMCs; alternative splicing and pathway analysis |
Nature communications |
High |
28799539
|
| 2018 |
SRSF1 promotes NMD by increasing UPF1 binding to mRNAs when SRSF1 is positioned downstream of a PTC; this mechanism bypasses UPF2 recruitment, is enhanced by splicing/EJC deposition, and resembles EJC-dependent NMD. |
UV-crosslinking RNA-IP for UPF1 binding; NMD reporter assays with SRSF1 tethered downstream of PTC; UPF2-independent mechanism demonstration |
Cell reports |
High |
29768215
|
| 2018 |
PP1 dephosphorylates the SRSF1 RS domain; two electrostatic residues in helix α2 and a hydrophobic residue in helix α1 of RRM1 constitute the PP1 binding surface; disruption of this interaction reduces RS domain phosphorylation and increases SRSF1 diffusion from speckles, shifting alternative splicing patterns. |
NMR spectroscopy to identify PP1-binding surface; mutagenesis of identified residues; phosphorylation state and localization analysis; alternative splicing assays |
The Journal of biological chemistry |
High |
30185622
|
| 2018 |
SRSF1 modulates PTPMT1 alternative splicing; reduced SRSF1 upon irradiation favors the short PTPMT1 isoform, which promotes AMPK phosphorylation and DNA double-strand breaks, sensitizing cancer cells to radiation. |
SRSF1 knockdown with RNA-seq; irradiation assays; AMPK phosphorylation measurement; tumor xenograft radiosensitivity |
EBioMedicine |
Medium |
30429088
|
| 2019 |
SRSF1 promotes gliomagenesis by switching the alternative splicing of MYO1B to produce a membrane-localized oncogenic isoform (MYO1B-fl) in a position-dependent manner; MYO1B-fl activates PDK1/AKT and PAK/LIMK pathways to increase tumorigenic potential. |
RNA-Seq; motif analysis; SRSF1 KD with functional rescue using MYO1B isoforms; pathway activation assays; in vivo glioma model |
The Journal of clinical investigation |
High |
30481162
|
| 2019 |
T cell-restricted Srsf1 knockout mice develop systemic autoimmunity with increased mTORC1 activity and reduced PTEN expression; SRSF1 overexpression rescues PTEN and suppresses mTORC1 activation, establishing a direct SRSF1-PTEN-mTORC1 regulatory axis in T cells. |
Conditional T cell-specific Srsf1 knockout mice; flow cytometry; mTOR pathway inhibition with rapamycin; SRSF1 overexpression rescue in human T cells |
The Journal of clinical investigation |
High |
31487268
|
| 2021 |
The RRM1 of SRSF1 binds preferentially to a CN motif (N = any nucleotide); a single E87N mutation in RRM1 enables binding to uridines and activates SMN exon 7 inclusion; the flexible inter-RRM linker allows RRM1 to bind RNA on both sides of the RRM2 binding site, revealing a bimodal mode of interaction. |
NMR solution structure of RRM1-RNA complex; site-directed mutagenesis (E87N); in vitro and cell-based SMN exon 7 splicing assays; RNA binding measurements |
Nature communications |
High |
33462199
|
| 2021 |
SRSF1 inhibits autophagy by (1) promoting splicing of Bcl-xL long isoform that interacts with Beclin1 to disrupt the Beclin1-PIK3C3 complex, and (2) directly interacting with PIK3C3 to prevent Beclin1-PIK3C3 interaction; SRSF1 itself is degraded by autophagy via interaction with LC3-II, creating a positive feedback loop. |
Autophagosome/LC3-II quantification; co-immunoprecipitation of Beclin1-PIK3C3; alternative splicing analysis of Bcl-x; SRSF1-LC3 interaction by co-IP |
Signal transduction and targeted therapy |
High |
33664238
|
| 2021 |
SRSF1 nucleo-cytoplasmic shuttling is required for efficient translation of a subset of mRNAs involved in multiciliogenesis; a knock-in mouse model with nuclear-retained SRSF1 (NRS insertion) shows small body size, hydrocephalus, and immotile sperm due to ciliary defects. |
Genome-editing knock-in of nuclear retention signal (NRS) in Srsf1; polyribosome profiling; proteomics; ciliary structure and motility assays |
eLife |
High |
34338635
|
| 2021 |
SRSF1 is recruited by U1 snRNP via direct contact with U1 snRNA stem-loop 3, independently of exon sequences and separately from ESE binding; this exon-independent recruitment is required for splicing and underlies exon definition. |
Single-molecule co-localization assays; structural NMR and cross-linking analysis; functional splicing assays with U1 snRNA stem-loop 3 mutations |
The EMBO journal |
High |
34779515
|
| 2021 |
SRSF1 is essential for hepatocyte function through maintenance of genome stability; SRSF1 depletion in mouse liver causes excessive R-loop formation, DNA damage, global inhibition of mRNA transcription and protein synthesis, lipid accumulation (via impaired lipid metabolism/trafficking), and NASH-like pathology with necroptotic cell death. |
Liver-specific Srsf1 knockout mice; hepatocyte transcriptome, proteome, RNA-binding analysis (eCLIP); R-loop detection assays; lipid staining; histopathology |
Nature communications |
High |
36759613
|
| 2021 |
SRSF1-dependent nuclear export of pathological C9ORF72-repeat transcripts is a key mechanism in ALS; partial SRSF1 depletion inhibits repeat RNA nuclear export and confers neuroprotection in C9ORF72-ALS patient-derived neurons and Drosophila models. |
Gene therapy-based SRSF1 depletion; genome-wide RNA sequencing in patient-derived neurons and Drosophila; functional motor neuron assays |
Molecular neurodegeneration |
Medium |
34376242
|
| 2021 |
SRSF1 and SRSF7 bind to a clustered motif region (CAR-N) in the intronless lncRNA NKILA to recruit the TREX complex (via UAP56 and ALYREF) for nuclear export via the TAP pathway; removal of CAR-N causes nuclear retention and abolishes NKILA's function in inhibiting breast cancer cell migration. |
In vitro RNP purification with mass spectrometry; siRNA screening; RNA-IP; protein-IP; knock-in models with CAR-N deletion |
Nucleic acids research |
High |
34096602
|
| 2021 |
SRSF1 is required for satellite cell proliferation and functional neuromuscular junction (NMJ) formation in postnatal mice; conditional deletion in myogenic progenitors prevents NMJ maturation, causing muscle weakness and premature death, associated with disrupted tissue-specific alternative splicing. |
Myogenic progenitor-specific Srsf1 conditional knockout mice; RNA-seq of alternative splicing; NMJ morphology and electrophysiology; satellite cell proliferation assays |
Stem cell reports |
High |
32888503
|
| 2023 |
SRSF1 activates MAPK signaling by upregulating IL1R1 through alternative-splicing-regulated mRNA stability; SRSF1 is destabilized via negative feedback in normal epithelial cells expressing KRASG12D; hyperactive MYC overrides this negative feedback to facilitate PDAC tumorigenesis. |
Pancreas-specific SRSF1 transgenic and conditional KO mice; KRASG12D mouse model; pancreas organoids; RNA-seq; MAPK pathway assays; MYC-SRSF1 interaction analysis |
Cancer discovery |
High |
37098965
|
| 2023 |
PRMT1 methylates SRSF1, which is critical for SRSF1 phosphorylation and RNA binding, and promotes exon inclusion in breast cancer; a selective PRMT1 inhibitor (iPRMT1) reduces SRSF1 arginine methylation, exon inclusion, and cancer cell growth. |
PRMT1 methylome profiling; in vitro methylation assays; phosphorylation assays after PRMT1 inhibition; RNA binding assays; tumor growth assays |
Cell reports |
High |
37938975
|
| 2024 |
SRSF1 interacts physically with FANCD2 and stimulates FANCD2 monoubiquitination in an RNA-dependent manner; monoubiquitinated FANCD2 in turn is crucial for assembly of the SRSF1-NXF1 nuclear export complex and mRNA export; SRSF1 cancer-associated mutants fail to interact with FANCD2, leading to R-loop accumulation. |
Co-immunoprecipitation of SRSF1-FANCD2; monoubiquitination assays; mRNA export measurements; R-loop detection; cancer-associated SRSF1 mutant analysis |
Cell reports |
High |
38165804
|