Affinage

RAI1

Retinoic acid-induced protein 1 · UniProt Q7Z5J4

Round 2 corrected
Length
1906 aa
Mass
203.4 kDa
Annotated
2026-04-28
130 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAI1 is a dosage-sensitive nuclear transcriptional activator essential for neurodevelopment, circadian rhythmicity, and energy homeostasis. It localizes to chromatin via a C-terminal ePHD/ADD-like domain and a conserved nucleosome-binding region, occupies active promoters in a neuronal activity-dependent manner, and directly transactivates targets including CLOCK and BDNF enhancer elements (PMID:22578325, PMID:32783930, PMID:24205348). Haploinsufficiency of RAI1 causes Smith–Magenis syndrome, while its overexpression produces Potocki–Lupski syndrome features, reflecting strict copy-number thresholds for normal CNS function (PMID:12652298, PMID:17024248). Cell-type-specific conditional knockouts demonstrate that RAI1 in hypothalamic neurons governs body weight, while its activity in cortical excitatory and inhibitory neurons controls homeostatic synaptic scaling, social behavior, and learning within a postnatal critical window (PMID:27693255, PMID:30275311, PMID:32783930).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 High

    Identification of a physical and functional partnership between yeast Rai1p and the nuclear exoribonuclease Rat1p established the founding biochemical activity of the Rai1 family — stabilizing and stimulating 5′→3′ exoribonuclease activity and participating in rRNA processing.

    Evidence Yeast two-hybrid, co-purification, in vitro exoribonuclease stimulation assay, synthetic lethality with rat1-1(ts), Northern blot rRNA analysis in S. cerevisiae

    PMID:10805743

    Open questions at the time
    • Whether mammalian RAI1 retains exoribonuclease-stimulating or pyrophosphohydrolase activity was unknown
    • Relevance of the Rat1 partnership to metazoan RAI1 function not tested
  2. 2003 High

    Cloning of human RAI1 and discovery that truncating mutations in RAI1 alone are sufficient to produce Smith–Magenis syndrome established RAI1 haploinsufficiency as the molecular basis for SMS, separating it from the broader 17p11.2 contiguous gene deletion.

    Evidence cDNA cloning, mutation screening of non-deletion SMS patients identifying frameshift mutations, RT-PCR expression profiling

    PMID:12652298 PMID:12837267

    Open questions at the time
    • Molecular function of RAI1 protein in mammalian cells was entirely uncharacterized
    • No structural or biochemical data for mammalian RAI1
  3. 2005 High

    Demonstration that RAI1 is a nuclear protein with intrinsic transcriptional activation activity, and that heterozygous Rai1-null mice recapitulate SMS phenotypes, provided the first functional classification of RAI1 as a dosage-sensitive transcriptional activator.

    Evidence Gene-targeted Rai1-null mice, GFP-Rai1 nuclear localization, GAL4-Rai1 transactivation reporter assay

    PMID:15746153

    Open questions at the time
    • Target genes of RAI1 transactivation unknown
    • Chromatin-binding mechanism unresolved
    • Pathway specificity of dosage sensitivity not addressed
  4. 2006 High

    Genetic rescue of the dup(17)(p11.2) mouse phenotype by normalizing Rai1 copy number proved that RAI1 is the critical dosage-sensitive gene underlying both deletion (SMS) and duplication (Potocki–Lupski) syndromes.

    Evidence Compound heterozygous Dp(11)17/Rai1-null mouse genetics with behavioral and physical phenotyping

    PMID:17024248

    Open questions at the time
    • Cellular and circuit-level mechanisms of dosage sensitivity not identified
    • Whether dosage effects are transcriptional or post-transcriptional unknown
  5. 2009 High

    Crystal structures of the S. pombe Rat1–Rai1 complex and free Rai1/Dom3Z revealed the structural basis by which Rai1 activates Rat1 exoribonuclease activity, and uncovered an intrinsic pyrophosphohydrolase activity in the Rai1 active-site pocket — the first such eukaryotic activity — broadening the enzymatic repertoire of the family.

    Evidence X-ray crystallography (2.0–2.2 Å), in vitro exoribonuclease and pyrophosphohydrolase assays, active-site mutagenesis

    PMID:19194460

    Open questions at the time
    • Whether mammalian RAI1 retains enzymatic activity or only transcriptional function was unclear
    • Structural basis for mammalian RAI1 chromatin interaction not addressed
  6. 2010 High

    Domain-dissection of human RAI1 established that N-terminal truncation mutations displace the protein from the nucleus and abolish BDNF enhancer transactivation, while C-terminal missense mutations retain nuclear localization but still lose transactivation, defining separable localization and activation domains.

    Evidence Immunofluorescence, luciferase reporter assays with wild-type and mutant RAI1 constructs, patient lymphoblastoid cell fractionation

    PMID:20738874 PMID:23028815

    Open questions at the time
    • Identity of direct chromatin-binding domain not resolved
    • Genome-wide target repertoire unknown
  7. 2012 High

    Discovery that RAI1 directly activates the CLOCK promoter and that RAI1 haploinsufficiency disrupts downstream circadian gene oscillation established RAI1 as a transcriptional regulator of the mammalian circadian clock.

    Evidence CLOCK promoter-luciferase reporter, RT-qPCR of circadian genes in SMS patient fibroblasts and Rai1+/− mouse hypothalamus

    PMID:22578325

    Open questions at the time
    • Whether RAI1 binds CLOCK promoter chromatin directly (ChIP) not shown
    • Mechanism linking RAI1 to circadian period length not fully resolved
  8. 2013 Medium

    Identification of a conserved ePHD/ADD-like domain and a nucleosome-binding region in RAI1, combined with demonstration of direct nucleosome core binding, provided the first chromatin-reader mechanism for how RAI1 engages its genomic targets; concurrently, free-running circadian period shortening in Rai1+/− mice confirmed RAI1 as the gene responsible for SMS-associated circadian defects.

    Evidence In vitro nucleosome pull-down, yeast two-hybrid for ePHD topology, free-running locomotor activity in constant darkness across multiple mouse models

    PMID:23703963 PMID:24205348

    Open questions at the time
    • ePHD/nucleosome-binding interaction lacks structural resolution at atomic level
    • Histone mark specificity of ePHD reader not determined
    • In vivo ChIP validation of nucleosome-binding region absent
  9. 2015 High

    Crystal structures of fungal Rai1 homologs bound to RNA substrates revealed how active-site tunnel geometry dictates substrate specificity among pyrophosphohydrolase, decapping, and triphosphonucleotide hydrolase activities, unifying diverse cap-removal functions in a single catalytic locus.

    Evidence X-ray crystallography with RNA oligonucleotides, structure-based mutagenesis, PPH/decapping/exonuclease activity assays

    PMID:26101253

    Open questions at the time
    • Catalytic activities demonstrated for fungal orthologs; metazoan RAI1 enzymatic activity not confirmed
    • In vivo RNA substrates of Rai1 cap-removal not identified
  10. 2016 High

    Genome-wide ChIP-seq demonstrated that Rai1 preferentially occupies active promoters in mouse brain, and cell-type-specific conditional knockouts revealed circuit-level division of labor: hypothalamic Rai1 controls energy balance while cortical/subcortical Rai1 governs learning and motor function.

    Evidence ChIP-seq in mouse brain, Cre/loxP conditional knockouts in inhibitory, excitatory, Sim1+, and SF1+ neurons with behavioral phenotyping

    PMID:27693255

    Open questions at the time
    • Cofactors mediating RAI1 recruitment to active promoters unidentified
    • Mechanism by which RAI1 activates transcription at bound promoters unknown
  11. 2018 High

    Temporal genetic rescue experiments defined a postnatal critical window (~3–4 weeks) during which restoring Rai1 dosage normalizes neural gene expression and social behavior, demonstrating that RAI1 function is required during a developmental period and not merely for ongoing maintenance.

    Evidence Tet-inducible Rai1 reactivation at defined postnatal ages, RNA-seq, social interaction testing, dendritic spine analysis

    PMID:30275311

    Open questions at the time
    • Molecular basis of the critical window closure unknown
    • Whether the window applies to all SMS phenotypes or only social behavior untested
  12. 2020 High

    Two advances converged: (1) structural and biochemical demonstration that DXO/Rai1 enzymes remove non-canonical FAD and CoA caps from RNA, expanding the cap-removal repertoire; and (2) dynamic ChIP-seq and nascent transcriptomics showing RAI1 chromatin occupancy responds to neuronal activity changes and is required for homeostatic synaptic scaling, connecting RAI1 to activity-dependent gene regulation and synaptic plasticity.

    Evidence X-ray crystallography (DXO–FADP, Rai1–FADP), in vitro deFADding/deCoAping assays, DXO-KO cells; EU-seq, dynamic ChIP-seq, whole-cell patch clamp in Rai1-deficient neurons

    PMID:32374864 PMID:32783930

    Open questions at the time
    • Whether mammalian RAI1 (as opposed to DXO) retains deFADding/deCoAping activity in neurons is untested
    • Specific activity-dependent target genes directly controlled by RAI1 chromatin binding not fully catalogued
    • Structural basis for mammalian RAI1 chromatin engagement still lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: whether mammalian RAI1 retains any enzymatic (cap-removal) activity or functions exclusively as a transcription factor; the structural basis of RAI1's ePHD-mediated chromatin reading and histone-mark specificity; the identity of RAI1's cofactors and the transcriptional complex it operates within; and the molecular mechanism defining the postnatal critical window for RAI1-dependent circuit maturation.
  • No high-resolution structure of mammalian RAI1 available
  • No identified cofactors or chromatin-remodeling complex partners
  • Enzymatic versus transcriptional roles in mammalian neurons not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0016787 hydrolase activity 3 GO:0003677 DNA binding 2 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 4
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-112316 Neuronal System 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-4839726 Chromatin organization 3 R-HSA-1266738 Developmental Biology 2
Partners
BDNFCLOCKRAT1XRN2

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 S. cerevisiae Rai1p (YGL246c) physically binds the nuclear 5'→3' exoribonuclease Rat1p and stabilizes its in vitro exoribonuclease activity. Deletion of RAI1 is synthetically lethal with the rat1-1(ts) mutation, placing Rai1p as a functional partner of Rat1p in nuclear RNA processing and 5.8S rRNA maturation. Yeast two-hybrid, co-purification, in vitro exoribonuclease assay, genetic epistasis (synthetic lethality), Northern blot rRNA analysis Molecular and cellular biology High 10805743
2003 RAI1 encodes a nuclear protein highly expressed in neuronal tissues; the human gene comprises six exons producing a 7.6-kb mRNA and contains a polymorphic CAG repeat coding for a polyglutamine stretch in the N-terminal domain. cDNA cloning, RT-PCR expression profiling, genomic sequencing Genomics Medium 12837267
2003 Dominant frameshift mutations causing protein truncation in RAI1 are sufficient to produce Smith-Magenis syndrome features in the absence of 17p11.2 deletions, establishing RAI1 haploinsufficiency as the molecular basis for SMS. Sequencing of RAI1 in non-deletion SMS patients; frameshift mutation identification Nature genetics High 12652298
2004 Bioinformatics analysis of RAI1 protein sequence identified a conserved zinc finger-like plant homeodomain (PHD) at the C-terminus, homologous to trithorax-group chromatin-based transcription regulators, suggesting RAI1 functions in transcriptional control through a multi-protein chromatin-regulatory complex. Bioinformatics/comparative genomics (human–mouse ortholog alignment); PHD domain identification Human genetics Low 15565467
2005 Heterozygous Rai1 null mice (generated by gene targeting with lacZ insertion) recapitulate SMS features including obesity and craniofacial abnormalities. GFP-Rai1 fusion protein localizes to the nucleus and the GAL4-Rai1 fusion has transactivation activity, demonstrating that Rai1 is a nuclear transcriptional activator. Gene targeting/knockout mice, X-gal staining, GFP subcellular localization, GAL4 transactivation reporter assay Human molecular genetics High 15746153
2006 Restoring normal disomic Rai1 dosage in Dp(11)17/+ mice by combining the duplication with a Rai1 null allele rescues the complex physical and behavioral phenotypes, demonstrating that RAI1 copy number is the primary dosage-sensitive determinant of both SMS and dup(17)(p11.2) phenotypes. Compound heterozygous mouse genetics; behavioral and physical phenotyping of Dp(11)17/Rai1(-) mice The Journal of clinical investigation High 17024248
2007 Rai1 homozygous null mice display severe learning and motor deficits, hind limb clasping, overt seizures, and context/tone-dependent learning deficits. X-gal staining reveals Rai1 is predominantly expressed in hippocampal and cerebellar neurons, and Rai1 functions in a dosage-sensitive manner in the CNS. Behavioral testing battery (locomotion, EEG, context/tone fear conditioning), X-gal staining of Rai1+/- brain sections Human molecular genetics High 17517686
2008 Rai1-transgenic mice overexpressing Rai1 >1.5-fold show growth retardation, increased locomotor activity, abnormal anxiety behavior, altered gait, decreased grip strength, and dominant social behavior; homozygous transgenic mice show dosage-dependent exacerbation including severe neurological deficits, confirming that RAI1 operates with strict dosage thresholds for normal development. Transgenic mouse overexpression (hemizygous and homozygous), behavioral phenotyping, grip strength, gait analysis European journal of human genetics High 18285828
2009 Crystal structures of S. pombe Rat1 in complex with Rai1 (2.2 Å), and of Rai1 and murine Dom3Z alone (2.0 Å) reveal the molecular mechanism by which Rai1 activates Rat1 exoribonuclease activity and enables Rat1 to degrade RNAs with stable secondary structures. A conserved active-site pocket in Rai1/Dom3Z with three acidic residues coordinates a divalent cation; mutagenesis and biochemical assays demonstrate that Rai1 possesses pyrophosphohydrolase activity toward 5′-triphosphorylated RNA — the first demonstration of this activity in eukaryotes. X-ray crystallography, in vitro exoribonuclease assay, pyrophosphohydrolase activity assay, active-site mutagenesis Nature High 19194460
2010 Full-length human RAI1 protein localizes to the nucleus and activates transcription of a reporter gene. Frameshift truncation mutations (N-terminal half) cause cytoplasmic mislocalization and loss of transactivation of BDNF enhancer; missense mutations in the C-terminal half retain nuclear localization but abolish transactivation. Transcription factor activity and nuclear localization signals reside in distinct protein domains. Western blot, immunofluorescence localization, luciferase reporter transactivation assay with wild-type and mutant RAI1 constructs BMC molecular biology High 20738874
2012 RAI1 directly regulates transcription of CLOCK, a master circadian oscillator gene. Haploinsufficiency of RAI1 in SMS patient fibroblasts and Rai1+/- mouse hypothalamus disrupts circadian clock gene expression including PER2, PER3, CRY1, and BMAL1, demonstrating RAI1 as a positive transcriptional regulator of CLOCK and a critical component of the mammalian circadian oscillator. Luciferase promoter reporter assay (CLOCK promoter), RT-qPCR of circadian genes in patient fibroblasts and mouse hypothalamus, circadian gene expression profiling American journal of human genetics High 22578325
2012 SMS patient-derived lymphoblastoid cells carrying RAI1 c.3103insC mutation show the mutant truncated protein in cytoplasmic fractions while wild-type RAI1 localizes to chromatin-bound and nuclear matrix fractions, confirming that N-terminal truncations of RAI1 displace the protein from chromatin and abolish BDNF enhancer-directed transactivation. Subcellular fractionation (chromatin-bound, nuclear matrix, cytoplasmic), immunoblot, BDNF-luciferase reporter in patient lymphoblastoid cells PloS one High 23028815
2013 RAI1 protein contains a C-terminal ePHD/ADD-like chromatin-binding domain and a novel nucleosome-binding region (NBR) that is highly conserved in vertebrates. In vitro and yeast experiments show the ePHD/ADD-like domain adopts a cross-braced zinc finger topology. The conserved NBR of RAI1 directly binds the nucleosome core and histones. In vitro pull-down (nucleosome core binding), yeast two-hybrid, phylogenetic/domain analysis PloS one Medium 24205348
2013 Free-running circadian period lengths are shortened in Rai1+/- mice (gene knock-out) and Df(11)17-2/+ deletion mice but not in Dexras1+/- mice, indicating that Rai1 is the primary gene underlying circadian period defects in Smith-Magenis syndrome models. Free-running period length measurement (locomotor activity in constant dark) in multiple mouse models American journal of medical genetics. Part A High 23703963
2014 Knockdown of Rai1 in Xenopus laevis/tropicalis using antisense morpholinos causes midface hypoplasia, malformed mouth, aberrant neural crest cell migration, reduced facial cartilage, abnormal axon patterns, decreased forebrain ventricle size, decreased bdnf expression, and increased forebrain apoptosis, revealing a conserved developmental role for Rai1 in neural crest-dependent craniofacial development and neuronal survival. Antisense morpholino knockdown, in situ hybridization, immunostaining, TUNEL apoptosis assay in Xenopus embryos Mechanisms of development High 24878353
2015 Crystal structures of fungal Rai1 homologs bound to RNA oligonucleotides reveal differences in RNA-binding modes that underlie distinct activity profiles (pyrophosphohydrolase vs. triphosphonucleotide hydrolase). Structure-based mutations of poorly conserved residues contacting RNA substantially alter enzymatic activities, establishing the active-site tunnel as the single locus for PPH, decapping, and exonuclease activities. X-ray crystallography, structure-based mutagenesis, RNA enzyme activity assays (PPH, decapping, 5'→3' exonuclease, TPH) Nucleic acids research High 26101253
2016 Rai1 preferentially occupies DNA regions near active promoters (ChIP-seq in mouse brain) and promotes expression of genes involved in circuit assembly and neuronal communication. Pan-neural Rai1 loss causes deficits in motor function, learning, and food intake; Rai1 loss in inhibitory neurons or subcortical glutamatergic neurons causes learning deficits, while Rai1 loss in Sim1+ or SF1+ hypothalamic cells causes obesity. ChIP-seq (Rai1 chromatin occupancy), conditional Cre/loxP neuron-type-specific knockouts, behavioral testing (motor, learning, feeding) Neuron High 27693255
2018 Normalizing Rai1 levels in Rai1 heterozygous mice at 3–4 weeks postnatal (early adolescence) corrects expression of neural developmental pathway genes and fully reverses a social interaction deficit; Rai1 reactivation at 7–8 weeks is not beneficial, defining a postnatal critical window. Correct Rai1 dosage is required in both excitatory and inhibitory neurons for proper social interaction. Conditional Rai1 reactivation (tet-inducible allele) at defined postnatal timepoints, RNA-seq, social interaction behavioral testing, dendritic spine quantification, optogenetics Proceedings of the National Academy of Sciences of the United States of America High 30275311
2020 DXO/Rai1 enzymes remove FAD and dephospho-CoA (dpCoA) non-canonical caps from RNA (deFADding and deCoAping activities). Crystal structures of mammalian DXO with 3′-FADP or CoA, and fission yeast Rai1 with 3′-FADP, show FAD and CoA adopt folded conformations in the active-site tunnel; the flavin of FAD and pantetheine of CoA contact the same region, with conformational changes accommodating different caps. FAD-capped RNAs (<200 nt) are detected in human cells and stabilized in DXO-null cells. X-ray crystallography (DXO–FADP, DXO–CoA, Rai1–FADP complexes), in vitro deFADding/deCoAping enzyme assays, FAD-capQ detection in human cells, DXO knockout cells Nucleic acids research High 32374864
2020 RAI1 binds dynamically to chromatin near active promoters in response to changes in neuronal network activity and is required for activity-dependent nascent transcription. RAI1 suppresses synaptic upscaling in naive networks while promoting upscaling triggered by activity silencing; Rai1-deficient neurons show altered electrophysiological properties consistent with defective homeostatic synaptic plasticity. Nascent RNA sequencing (EU-seq), ChIP-seq (dynamic chromatin occupancy), whole-cell patch clamp electrophysiology in Rai1-deficient neurons Cell reports High 32783930
2021 ALKBH5-mediated m6A demethylation of pri-miR-194-2 inhibits miR-194-2 biogenesis in an m6A/DGCR8-dependent manner; RAI1 is the primary target of miR-194-2. RAI1 enhances transcription of Hippo pathway upstream genes by binding to their 3′UTR and suppresses YAP/TAZ nuclear translocation, functioning as a transcriptional enhancer in the Hippo pathway. m6A-seq, DGCR8 RIP, miRNA target validation (luciferase 3′UTR reporter), ChIP/RNA pull-down (RAI1 binding to 3′UTR), YAP/TAZ nuclear translocation assay, in vitro and xenograft models Oncogene Medium 34312488

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Biological insights from 108 schizophrenia-associated genetic loci. Nature 5878 25056061
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2010 An atlas of combinatorial transcriptional regulation in mouse and man. Cell 573 20211142
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2011 Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease. PLoS genetics 422 21738487
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2013 Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. Stroke 269 24262325
1994 Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. The Journal of clinical investigation 264 8132773
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2003 Mutations in RAI1 associated with Smith-Magenis syndrome. Nature genetics 244 12652298
2009 A daily SMS reminder increases adherence to asthma treatment: a three-month follow-up study. Respiratory medicine 218 19854632
1987 Effect of the somatostatin analogue sandostatin (SMS 201-995) on gastrointestinal, pancreatic and biliary function and hormone release in normal men. Digestion 217 2883060
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2009 Computerized Automated Reminder Diabetes System (CARDS): e-mail and SMS cell phone text messaging reminders to support diabetes management. Diabetes technology & therapeutics 188 19848576
2009 Structure and function of the 5'-->3' exoribonuclease Rat1 and its activating partner Rai1. Nature 171 19194460
1988 Preoperative treatment of acromegaly with long-acting somatostatin analog SMS 201-995: shrinkage of invasive pituitary macroadenomas and improved surgical remission rate. The Journal of clinical endocrinology and metabolism 165 2903168
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2020 Comparative Application of BioID and TurboID for Protein-Proximity Biotinylation. Cells 146 32344865
2003 X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. European journal of human genetics : EJHG 146 14508504
2012 Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Molecular & cellular proteomics : MCP 145 22586326
2011 Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy. Proceedings of the National Academy of Sciences of the United States of America 133 22106271
1989 Direct inhibitory effects of a somatostatin analog, SMS 201-995, on AR4-2J cell proliferation via pertussis toxin-sensitive guanosine triphosphate-binding protein-independent mechanism. Endocrinology 129 2563240
2018 SHLD2/FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice. The EMBO journal 124 30154076
2001 Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA research : an international journal for rapid publication of reports on genes and genomes 123 11347906
2016 Short message service (SMS) reminders and real-time adherence monitoring improve antiretroviral therapy adherence in rural Uganda. AIDS (London, England) 115 26760452
2021 Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry. Proceedings of the National Academy of Sciences of the United States of America 113 34349018
2019 Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes & development 110 31753913
2007 Inhibition of sphingomyelin synthase (SMS) affects intracellular sphingomyelin accumulation and plasma membrane lipid organization. Biochimica et biophysica acta 106 17616479
1995 Two amino acids, located in transmembrane domains VI and VII, determine the selectivity of the peptide agonist SMS 201-995 for the SSTR2 somatostatin receptor. The EMBO journal 105 7882976
2000 Saccharomyces cerevisiae RAI1 (YGL246c) is homologous to human DOM3Z and encodes a protein that binds the nuclear exoribonuclease Rat1p. Molecular and cellular biology 103 10805743
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2022 EZH2 depletion potentiates MYC degradation inhibiting neuroblastoma and small cell carcinoma tumor formation. Nature communications 99 35013218
2017 CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality. Nucleic acids research 91 28977666
2005 RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions. Journal of medical genetics 91 15788730
1988 Inhibition of growth of two human pancreatic adenocarcinomas in vivo by somatostatin analog SMS 201-995. American journal of surgery 89 2893555
2002 Role for radA/sms in recombination intermediate processing in Escherichia coli. Journal of bacteriology 86 12446634
1989 Use of long-acting somatostatin analog SMS 201-995 in patients with pancreatic islet cell tumors. Digestive diseases and sciences 86 2537716
2004 Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome. Human genetics 85 15565467
2003 SmcR and cyclic AMP receptor protein coactivate Vibrio vulnificus vvpE encoding elastase through the RpoS-dependent promoter in a synergistic manner. The Journal of biological chemistry 84 12947096
2012 Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity. American journal of human genetics 79 22578325
1998 p27Kip1: a key mediator of retinoic acid induced growth arrest in the SMS-KCNR human neuroblastoma cell line. Oncogene 78 9681834
2002 Structure and evolution of the Smith-Magenis syndrome repeat gene clusters, SMS-REPs. Genome research 76 11997339
2000 CAG repeat length in RAI1 is associated with age at onset variability in spinocerebellar ataxia type 2 (SCA2). Human molecular genetics 74 10915763
2010 Cell phone short messaging service (SMS) for HIV/AIDS in South Africa: a literature review. Studies in health technology and informatics 73 20841743
2005 Inactivation of Rai1 in mice recapitulates phenotypes observed in chromosome engineered mouse models for Smith-Magenis syndrome. Human molecular genetics 73 15746153
2006 Single-molecule spectroelectrochemistry (SMS-EC). Journal of the American Chemical Society 72 16834364
2007 Rai1 deficiency in mice causes learning impairment and motor dysfunction, whereas Rai1 heterozygous mice display minimal behavioral phenotypes. Human molecular genetics 67 17517686
2018 Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men. American journal of respiratory cell and molecular biology 66 29077507
2012 The bHLH Rac Immunity1 (RAI1) Is Activated by OsRac1 via OsMAPK3 and OsMAPK6 in Rice Immunity. Plant & cell physiology 65 22437844
1996 Octapeptide somatostatin analog SMS 201-995 induces translocation of intracellular PTP1C to membranes in MCF-7 human breast adenocarcinoma cells. Endocrinology 62 8754775
1992 UK-14,304, R(-)-alpha-methyl-histamine and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanisms. European journal of pharmacology 59 1281776
2008 The domain responsible for sphingomyelin synthase (SMS) activity. Biochimica et biophysica acta 58 18694848
2006 Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2). The Journal of clinical investigation 58 17024248
2016 Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome. Neuron 56 27693255
2014 Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate insensitivity. Molecular genetics and metabolism 56 24863970
2013 LuxR homologue SmcR is essential for Vibrio vulnificus pathogenesis and biofilm detachment, and its expression is induced by host cells. Infection and immunity 53 23897607
2006 Replication arrest-stimulated recombination: Dependence on the RecA paralog, RadA/Sms and translesion polymerase, DinB. DNA repair 53 16904387
2009 Short message service (SMS) technology in alcohol research--a feasibility study. Alcohol and alcoholism (Oxford, Oxfordshire) 52 19482879
1990 Percoll density gradient centrifugation of rat pituitary tumor cells: a study of functional heterogeneity within and between tumors with respect to growth rates, prolactin production and responsiveness to the somatostatin analog SMS 201-995. European journal of cancer (Oxford, England : 1990) 52 2138476
1987 Effect of SMS 201-995, a long-acting somatostatin analogue, on the secretion and morphology of a pituitary growth hormone cell adenoma. Clinical endocrinology 51 2888549
2021 N6-methyladenosine demethylase ALKBH5 suppresses malignancy of esophageal cancer by regulating microRNA biogenesis and RAI1 expression. Oncogene 50 34312488
2013 A randomized controlled trial to assess adherence to allergic rhinitis treatment following a daily short message service (SMS) via the mobile phone. International archives of allergy and immunology 50 24248037
2009 A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) causes Snyder-Robinson syndrome. American journal of medical genetics. Part A 50 19206178
2008 How much is too much? Phenotypic consequences of Rai1 overexpression in mice. European journal of human genetics : EJHG 50 18285828
2015 Stating Appointment Costs in SMS Reminders Reduces Missed Hospital Appointments: Findings from Two Randomised Controlled Trials. PloS one 47 26366885
1994 Somatostatin receptor subtype SSTR2 mediates the inhibition of high-voltage-activated calcium channels by somatostatin and its analogue SMS 201-995. FEBS letters 47 7982482
2011 Regulation of cytotoxicity by quorum-sensing signaling in Vibrio vulnificus is mediated by SmcR, a repressor of hlyU. Journal of bacteriology 45 21398530
2011 Smith-Magenis syndrome: haploinsufficiency of RAI1 results in altered gene regulation in neurological and metabolic pathways. Expert reviews in molecular medicine 44 21545756
2003 Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia. Genomics 44 12837267
2010 Retinoic Acid Induced 1, RAI1: A Dosage Sensitive Gene Related to Neurobehavioral Alterations Including Autistic Behavior. Current genomics 43 21629438
2008 A consensus sequence for binding of SmcR, a Vibrio vulnificus LuxR homologue, and genome-wide identification of the SmcR regulon. The Journal of biological chemistry 42 18579523
2007 Identification and functional analysis of vibrio vulnificus SmcR, a novel global regulator. Journal of microbiology and biotechnology 42 18051765
2006 RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome. American journal of medical genetics. Part A 42 17041942
2016 Recombinational branch migration by the RadA/Sms paralog of RecA in Escherichia coli. eLife 40 26845522
1989 Somatostatin analogue SMS 201-995 (octreotide) as a possible solution to the dumping syndrome after gastrectomy or vagotomy. The British journal of surgery 40 2702445
1987 A comparison between the effects of SMS 201-995, bromocriptine and a combination of both drugs on hormone release by the cultured pituitary tumour cells of acromegalic patients. Clinical endocrinology 40 2888550
2019 Importance of OsRac1 and RAI1 in signalling of nucleotide-binding site leucine-rich repeat protein-mediated resistance to rice blast disease. The New phytologist 39 30919975
2017 RAI1 gene mutations: mechanisms of Smith-Magenis syndrome. The application of clinical genetics 38 29138588
2010 Crystal structure of SmcR, a quorum-sensing master regulator of Vibrio vulnificus, provides insight into its regulation of transcription. The Journal of biological chemistry 38 20178981
2011 Molecular analysis of the Retinoic Acid Induced 1 gene (RAI1) in patients with suspected Smith-Magenis syndrome without the 17p11.2 deletion. PloS one 37 21857958
2006 Transcriptional regulatory cascade for elastase production in Vibrio vulnificus: LuxO activates luxT expression and LuxT represses smcR expression. The Journal of biological chemistry 36 16971386
2020 DXO/Rai1 enzymes remove 5'-end FAD and dephospho-CoA caps on RNAs. Nucleic acids research 35 32374864
2007 Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike. American journal of human genetics 34 17273973
2013 The fur-iron complex modulates expression of the quorum-sensing master regulator, SmcR, to control expression of virulence factors in Vibrio vulnificus. Infection and immunity 33 23716618
1988 SMS 201-995 and provocation tests in preparation of patients with carcinoids for surgery or hepatic arterial embolization. Anesthesia and analgesia 32 2461665
2015 Nonrecurrent 17p11.2p12 Rearrangement Events that Result in Two Concomitant Genomic Disorders: The PMP22-RAI1 Contiguous Gene Duplication Syndrome. American journal of human genetics 31 26544804
2012 RAI1 transcription factor activity is impaired in mutants associated with Smith-Magenis Syndrome. PloS one 31 23028815
2020 RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling. Cell reports 30 32783930
2010 Direct interaction between quorum-sensing regulator SmcR and RNA polymerase is mediated by integration host factor to activate vvpE encoding elastase in Vibrio vulnificus. The Journal of biological chemistry 30 20110369
2010 Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1) mutations associated with Smith-Magenis Syndrome. BMC molecular biology 30 20738874
2002 The apoptotic effect of somatostatin analogue SMS 201-995 on human lymphocytes. Journal of neuroimmunology 30 12446025
2015 Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome. The Journal of clinical endocrinology and metabolism 29 25781356
1990 Effects of SMS 201-995 on basal and stimulated pancreatic secretion in rats. Endocrinology 29 2361474
2005 Diagnostic FISH probes for del(17)(p11.2p11.2) associated with Smith-Magenis syndrome should contain the RAI1 gene. American journal of medical genetics. Part A 28 15690371
2001 RAI1 is a novel polyglutamine encoding gene that is deleted in Smith-Magenis syndrome patients. Gene 28 11404004
2020 Implementation of a 4Pi-SMS super-resolution microscope. Nature protocols 26 33328610
2017 Health promotion via SMS improves hypertension knowledge for deaf South Africans. BMC public health 26 28821288
2014 Retinoic acid induced-1 (Rai1) regulates craniofacial and brain development in Xenopus. Mechanisms of development 26 24878353
2014 Pharmacologic inhibition of sphingomyelin synthase (SMS) activity reduces apolipoprotein-B secretion from hepatocytes and attenuates endotoxin-mediated macrophage inflammation. PloS one 26 25032960
2018 Early adolescent Rai1 reactivation reverses transcriptional and social interaction deficits in a mouse model of Smith-Magenis syndrome. Proceedings of the National Academy of Sciences of the United States of America 25 30275311
2014 Frequency of De Quervain's tenosynovitis and its association with SMS texting. Muscles, ligaments and tendons journal 25 24932451
2012 Evidence that the Vibrio vulnificus flagellar regulator FlhF is regulated by a quorum sensing master regulator SmcR. Microbiology (Reading, England) 25 22679105
1994 Effect of bromocriptine and SMS 201-995 on growth of human somatotrophic and non-functioning pituitary adenoma cells in vitro. European journal of endocrinology 25 8124483
1990 The effect of the E2 prostaglandin enprostil, and the somatostatin analogue SMS 201 995, on the growth of a human gastric cell line, MKN45G. International journal of cancer 25 2105279
1988 The effect of a somatostatin analogue (SMS 201-995, Sandostatin) on the concentration of phosphoribosyl pyrophosphate and the activity of the pentose phosphate pathway in the early renal hypertrophy of experimental diabetes in the rat. Biochemical medicine and metabolic biology 25 2454125
2017 Activity and in vivo dynamics of Bacillus subtilis DisA are affected by RadA/Sms and by Holliday junction-processing proteins. DNA repair 24 28511132
2016 Identification of a RAI1-associated disease network through integration of exome sequencing, transcriptomics, and 3D genomics. Genome medicine 24 27799067
2013 Circadian abnormalities in mouse models of Smith-Magenis syndrome: evidence for involvement of RAI1. American journal of medical genetics. Part A 24 23703963
1986 Characterization of the in vivo and in vitro inhibition of gastrin secretion from gastrinoma by a somatostatin analogue (SMS 201-995). The American journal of medicine 24 2879448
2022 Variation in community structure and network characteristics of spent mushroom substrate (SMS) compost microbiota driven by time and environmental conditions. Bioresource technology 23 36089128
2009 The impact of spermine synthase (SMS) mutations on brain morphology. Neurogenetics 23 19277733
1989 Changes in expression of tyrosine hydroxylase immunoreactivity in human SMS-KCNR neuroblastoma following retinoic acid or phorbol ester-induced differentiation. Brain research. Molecular brain research 23 2568572
2019 Bacillus subtilis RecA interacts with and loads RadA/Sms to unwind recombination intermediates during natural chromosomal transformation. Nucleic acids research 22 31350886
2019 The complete loss of function of the SMS gene results in a severe form of Snyder-Robinson syndrome. European journal of medical genetics 22 31580924
2024 CuO/TiO2/MXene-Based Sensor and SMS-TENG Array Integrated Inspection Robots for Self-Powered Ethanol Detection and Alarm at Room Temperature. ACS sensors 21 38358362
2014 Identification of Nine New RAI1-Truncating Mutations in Smith-Magenis Syndrome Patients without 17p11.2 Deletions. Molecular syndromology 21 24715852
2015 Structural and biochemical studies of the distinct activity profiles of Rai1 enzymes. Nucleic acids research 20 26101253
2013 A phylogenetic study of SPBP and RAI1: evolutionary conservation of chromatin binding modules. PloS one 20 24205348
1995 Coupling of the human Y2 receptor for neuropeptide Y and peptide YY to guanine nucleotide inhibitory proteins in permeabilized SMS-KAN cells. Journal of neurochemistry 20 7830057
2023 Pentanucleotide Repeat Insertions in RAI1 Cause Benign Adult Familial Myoclonic Epilepsy Type 8. Movement disorders : official journal of the Movement Disorder Society 19 37994247