Gene Symbol: UPF3B
Description: UPF3B, regulator of nonsense mediated mRNA decay
Alias: HUPF3B, MRX62, MRXS14, RENT3B, UPF3BP1, UPF3BP2, UPF3BP3, UPF3X, Upf3p-X, regulator of nonsense transcripts 3B, UPF3 regulator of nonsense transcripts homolog B, UPF3B pseudogene 1, UPF3B pseudogene 2, UPF3B pseudogene 3, mental retardation, X-linked 62, nonsense mRNA reducing factor 3B, up-frameshift suppressor 3 homolog B, up-frameshift suppressor 3 homolog on chromosome X
Species: human
Products:     UPF3B

Top Publications

  1. Gehring N, Lamprinaki S, Kulozik A, Hentze M. Disassembly of exon junction complexes by PYM. Cell. 2009;137:536-48 pubmed publisher
    ..In cells depleted of PYM, EJCs accumulate on spliced mRNAs and EJC protein recycling is impaired. Hence, PYM is an EJC disassembly factor that acts both in vitro and in living cells, and that antagonizes important EJC functions. ..
  2. Serin G, Gersappe A, Black J, Aronoff R, Maquat L. Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4). Mol Cell Biol. 2001;21:209-23 pubmed
    ..The finding that hUpf3p-X is a shuttling protein provides additional indication that NMD has both nuclear and cytoplasmic components...
  3. Ivanov P, Gehring N, Kunz J, Hentze M, Kulozik A. Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways. EMBO J. 2008;27:736-47 pubmed publisher
    ..studies show that UPF1 can interact with the exon junction complex (EJC) alternatively through either UPF2 or UPF3b to become phosphorylated and to activate NMD...
  4. Chan W, Bhalla A, Le Hir H, Nguyen L, Huang L, Gecz J, et al. A UPF3-mediated regulatory switch that maintains RNA surveillance. Nat Struct Mol Biol. 2009;16:747-53 pubmed publisher
    ..we identify a regulatory mechanism acting on two related UPF (up-frameshift) factors crucial for NMD: UPF3A and UPF3B. This regulatory mechanism, which reduces the level of UPF3A in response to the presence of UPF3B, is relieved in ..
  5. Gehring N, Kunz J, Neu Yilik G, Breit S, Viegas M, Hentze M, et al. Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol Cell. 2005;20:65-75 pubmed
    ..These results are integrated into a nonlinear model for mammalian NMD involving alternative routes of entry that converge at a common requirement of UPF1. ..
  6. Chiu S, Serin G, Ohara O, Maquat L. Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1. RNA. 2003;9:77-87 pubmed
    ..Furthermore, hSmg5/7a copurifies with Upf1, Upf2, Upf3X, Smg1, and the catalytic subunit of protein phosphatase 2A...
  7. Tarpey P, Raymond F, Nguyen L, Rodriguez J, Hackett A, Vandeleur L, et al. Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nat Genet. 2007;39:1127-33 pubmed
    ..X chromosome in 250 families with X-linked mental retardation, we identified mutations in the UPF3 regulator of nonsense transcripts homolog B (yeast) (UPF3B) leading to protein truncations in three families: two with the Lujan-Fryns ..
  8. Kadlec J, Izaurralde E, Cusack S. The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3. Nat Struct Mol Biol. 2004;11:330-7 pubmed
    ..95 A of the complex between the interacting domains of human UPF2 and UPF3b, which are, respectively, a MIF4G (middle portion of eIF4G) domain and an RNP domain (ribonucleoprotein-type RNA-..
  9. Lykke Andersen J, Shu M, Steitz J. Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1. Science. 2001;293:1836-9 pubmed
    ..Significantly, RNPS1 triggers NMD when tethered to the 3' untranslated region of beta-globin mRNA, demonstrating its role as a subunit of the postsplicing complex directly involved in mRNA surveillance...

More Information


  1. Kim V, Kataoka N, Dreyfuss G. Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex. Science. 2001;293:1832-6 pubmed
    ..The splicing-dependent binding of hUpf3 to mRNAs before export, as part of the complex that assembles near exon-exon junctions, allows it to serve as a link between splicing and NMD in the cytoplasm. ..
  2. Lykke Andersen J, Shu M, Steitz J. Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell. 2000;103:1121-31 pubmed
    ..We describe three novel human proteins involved in NMD, hUpf2, hUpf3a, and hUpf3b. While in HeLa cell extracts these proteins are complexed with hUpf1, in intact cells hUpf3a and hUpf3b are ..
  3. Kashima I, Yamashita A, Izumi N, Kataoka N, Morishita R, Hoshino S, et al. Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay. Genes Dev. 2006;20:355-67 pubmed
    ..Here we show that SMG-1 binds to the mRNA-associated components of the EJC, Upf2, Upf3b, eIF4A3, Magoh, and Y14...
  4. Chamieh H, Ballut L, Bonneau F, Le Hir H. NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity. Nat Struct Mol Biol. 2008;15:85-93 pubmed
    ..The EJC proteins MAGOH, Y14 and eIF4AIII provide a composite binding site for UPF3b that serves as a bridge to UPF2 and UPF1...
  5. Gehring N, Neu Yilik G, Schell T, Hentze M, Kulozik A. Y14 and hUpf3b form an NMD-activating complex. Mol Cell. 2003;11:939-49 pubmed
    ..Here, we identify a conserved domain of hUpf3b that mediates an interaction with the EJC protein Y14...
  6. Buchwald G, Ebert J, Basquin C, Sauliere J, Jayachandran U, Bono F, et al. Insights into the recruitment of the NMD machinery from the crystal structure of a core EJC-UPF3b complex. Proc Natl Acad Sci U S A. 2010;107:10050-5 pubmed publisher
    ..b>UPF3b is the component of the surveillance complex that bridges the interaction with the EJC. Here, we report the 3...
  7. Sato H, Maquat L. Remodeling of the pioneer translation initiation complex involves translation and the karyopherin importin beta. Genes Dev. 2009;23:2537-50 pubmed publisher
    ..Our studies uncover a previously unappreciated role for IMPbeta and a novel paradigm for how newly synthesized messenger ribonucleoproteins (mRNPs) are matured. ..
  8. Lejeune F, Ishigaki Y, Li X, Maquat L. The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling. EMBO J. 2002;21:3536-45 pubmed
    ..Consistent with this evidence, we demonstrate that RNPS1, Y14, SRm160, REF/Aly, TAP, Upf3X and Upf2 are detected in the nuclear fraction on CBP80-bound but not eIF4E-bound mRNA...
  9. Raimondeau E, Bufton J, Schaffitzel C. New insights into the interplay between the translation machinery and nonsense-mediated mRNA decay factors. Biochem Soc Trans. 2018;46:503-512 pubmed publisher
    ..Our review summarizes our current understanding of the molecular function of the conserved NMD factors UPF3B and UPF1, and of the anti-NMD factor Poly(A)-binding protein, and their interactions with ribosomes translating ..
  10. Kamelgarn M, Chen J, Kuang L, Jin H, Kasarskis E, Zhu H. ALS mutations of FUS suppress protein translation and disrupt the regulation of nonsense-mediated decay. Proc Natl Acad Sci U S A. 2018;115:E11904-E11913 pubmed publisher
    ..Specifically, NMD-promoting factors UPF1 and UPF3b increased, whereas a negative NMD regulator, UPF3a, decreased, leading to the disruption of NMD autoregulation and ..
  11. Jin Z, Yu L, Geng J, Wang J, Jin X, Huang H. A novel 47.2 Mb duplication on chromosomal bands Xq21.1-25 associated with mental retardation. Gene. 2015;567:98-102 pubmed publisher
    ..Ten genes (i.e., ZNF711, SRPX2, RAB40AL, MID2, ACSL4, PAK3, UBE2A, UPF3B, CUL4B, and GRIA3) in the duplication interval have been associated with mental retardation...
  12. Lovrecic L, Rajar P, Volk M, Bertok S, Gnidovec Strazisar B, Osredkar D, et al. Diagnostic efficacy and new variants in isolated and complex autism spectrum disorder using molecular karyotyping. J Appl Genet. 2018;59:179-185 pubmed publisher
    ..3%). An interesting case of previously unreported partial UPF3B gene deletion was identified among the pathogenic CNVs...
  13. López Perrote A, Castaño R, Melero R, Zamarro T, Kurosawa H, Ohnishi T, et al. Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex. Nucleic Acids Res. 2016;44:1909-23 pubmed publisher
    ..Accordingly, we find that the interaction of UPF2 with UPF3b interferes with the assembly of the UPF2-eRF3 complex, and that UPF2 binds UPF3b more strongly than eRF3...
  14. Huang L, Low A, Damle S, KEENAN M, Kuntz S, Murray S, et al. Antisense suppression of the nonsense mediated decay factor Upf3b as a potential treatment for diseases caused by nonsense mutations. Genome Biol. 2018;19:4 pubmed publisher
    ..Among all of the NMD factors, Upf3b depletion is well tolerated, consistent with previous reports that UPF3B is not essential for development and ..
  15. MacDonald C, Grozdanov P. Nonsense in the testis: multiple roles for nonsense-mediated decay revealed in male reproduction. Biol Reprod. 2017;96:939-947 pubmed publisher
    ..is possibly due to increased expression of Upf3a in postmeiotic germ cells that antagonizes the functions of Upf3b and somehow favors long 3? UTR-mediated NMD...
  16. Baird T, Cheng K, Chen Y, Buehler E, Martin S, Inglese J, et al. ICE1 promotes the link between splicing and nonsense-mediated mRNA decay. elife. 2018;7: pubmed publisher
    ..Further, our data suggest that ICE1 uses a putative MIF4G domain to interact with exon junction complex (EJC) proteins and promotes the association of the NMD protein UPF3B with the EJC.
  17. Hauer C, Sieber J, Schwarzl T, Hollerer I, Curk T, Alleaume A, et al. Exon Junction Complexes Show a Distributional Bias toward Alternatively Spliced mRNAs and against mRNAs Coding for Ribosomal Proteins. Cell Rep. 2016;16:1588-1603 pubmed publisher
    ..of bona fide EJC binding sites across the transcriptome including all four RNA binding EJC components eIF4A3, BTZ, UPF3B, and RNPS1...
  18. Lykke Andersen J. Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay. Mol Cell Biol. 2002;22:8114-21 pubmed
    ..decay factor hUpf1, both in the presence and in the absence of the other hUpf proteins, hUpf2, hUpf3a, and hUpf3b. These data suggest that a human decapping complex may be recruited to mRNAs containing premature termination ..
  19. Huang L, Shum E, Jones S, Lou C, Dumdie J, Kim H, et al. A Upf3b-mutant mouse model with behavioral and neurogenesis defects. Mol Psychiatry. 2018;23:1773-1786 pubmed publisher
    ..In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention ..
  20. Ruepp M, Aringhieri C, Vivarelli S, Cardinale S, Paro S, Schumperli D, et al. Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export. Mol Biol Cell. 2009;20:5211-23 pubmed publisher
    ..These results reveal a novel function for the pre-mRNA 3' end processing factor CF I(m)68 in mRNA export. ..
  21. Geißler V, Altmeyer S, Stein B, Uhlmann Schiffler H, Stahl H. The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of Ddx17/p72 and Smg5 mRNA. Nucleic Acids Res. 2013;41:7875-88 pubmed publisher
    ..For NMD triggering, the adenosine triphosphate-binding activity of Ddx5 and the 3'-untranslated region of substrate mRNAs are essential. ..
  22. Addington A, Gauthier J, Piton A, Hamdan F, Raymond A, Gogtay N, et al. A novel frameshift mutation in UPF3B identified in brothers affected with childhood onset schizophrenia and autism spectrum disorders. Mol Psychiatry. 2011;16:238-9 pubmed publisher
  23. Kunz J, Neu Yilik G, Hentze M, Kulozik A, Gehring N. Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation. RNA. 2006;12:1015-22 pubmed
    The exon-junction complex (EJC) components hUpf3a and hUpf3b serve a dual function: They promote nonsense-mediated mRNA decay (NMD), and they also regulate translation efficiency...
  24. Kim Y, Furic L, DesGroseillers L, Maquat L. Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay. Cell. 2005;120:195-208 pubmed
    ..Unlike NMD, this mechanism does not involve pre-mRNA splicing and occurs when Upf2 or Upf3X is downregulated...
  25. Hug N, Cáceres J. The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance to the decay-inducing complex. Cell Rep. 2014;8:1845-1856 pubmed publisher
    ..Subsequently, an interaction with UPF2, UPF3b, and the exon junction complex induces the formation of the decay-inducing complex (DECID) and triggers NMD...
  26. Metze S, Herzog V, Ruepp M, Mühlemann O. Comparison of EJC-enhanced and EJC-independent NMD in human cells reveals two partially redundant degradation pathways. RNA. 2013;19:1432-48 pubmed publisher
    ..depend on UPF1 and SMG1, but detected transcript-specific differences with respect to the requirement for UPF2 and UPF3b, consistent with previously reported UPF2- and UPF3-independent branches of NMD...
  27. Lynch S, Nguyen L, Ng L, Waldron M, McDonald D, Gecz J. Broadening the phenotype associated with mutations in UPF3B: two further cases with renal dysplasia and variable developmental delay. Eur J Med Genet. 2012;55:476-9 pubmed publisher
    We present two brothers with mutations in UPF3B, an X-linked intellectual disability gene. Our family consists of two affected brothers and a carrier mother. Both affected brothers had renal dysplasia...
  28. Barbosa I, Haque N, Fiorini F, Barrandon C, Tomasetto C, Blanchette M, et al. Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly. Nat Struct Mol Biol. 2012;19:983-90 pubmed publisher
    ..We elucidated the initial step of EJC assembly and the duality of CWC22 function that hinders eIF4AIII from nonspecifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. ..
  29. Meng B, Lever A. Wrapping up the bad news: HIV assembly and release. Retrovirology. 2013;10:5 pubmed publisher
  30. Xu X, Zhang L, Tong P, Xun G, Su W, Xiong Z, et al. Exome sequencing identifies UPF3B as the causative gene for a Chinese non-syndrome mental retardation pedigree. Clin Genet. 2013;83:560-4 pubmed publisher
    ..In this study, we applied exome sequencing to identify the mutation p.R430X in UPF3B gene in an MR pedigree, which was validated by Sanger sequencing and completely cosegregated within this family...
  31. Hosoda N, Kim Y, Lejeune F, Maquat L. CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells. Nat Struct Mol Biol. 2005;12:893-901 pubmed
    ..An EJC includes the NMD factors Upf3 or Upf3X and Upf2, and Upf2 recruits Upf1...
  32. Leoyklang P, Suphapeetiporn K, Srichomthong C, Tongkobpetch S, Fietze S, Dorward H, et al. Disorders with similar clinical phenotypes reveal underlying genetic interaction: SATB2 acts as an activator of the UPF3B gene. Hum Genet. 2013;132:1383-93 pubmed publisher
    ..of SATB2, a transcription regulator and the other by heterozygous mutations leading to premature stop codons in UPF3B, encoding a member of the nonsense-mediated mRNA decay complex...
  33. Gehring N, Lamprinaki S, Hentze M, Kulozik A. The hierarchy of exon-junction complex assembly by the spliceosome explains key features of mammalian nonsense-mediated mRNA decay. PLoS Biol. 2009;7:e1000120 pubmed publisher
    ..Based on this systematic analysis of EJC assembly by the spliceosome, we propose a model of how a functional EJC is assembled in a strictly sequential and hierarchical fashion, including nuclear splicing-dependent and cytoplasmic steps. ..
  34. Lejeune F, Li X, Maquat L. Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities. Mol Cell. 2003;12:675-87 pubmed
    ..Furthermore, NMD factors Upf1, Upf2, and Upf3X coimmunopurify with the decapping enzyme Dcp2, the putative 5'-->3' exonuclease Rat1, the proven 5'-->3' ..
  35. Wilson K, Fortes P, Singh U, Ohno M, Mattaj I, Cerione R. The nuclear cap-binding complex is a novel target of growth factor receptor-coupled signal transduction. J Biol Chem. 1999;274:4166-73 pubmed
    ..Taken together, these data identify the CBC as a nuclear target for growth factor-coupled signal transduction and suggest novel mechanisms by which growth factors can influence gene expression and cell growth. ..
  36. Woeller C, Gaspari M, Isken O, Maquat L. NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA. EMBO Rep. 2008;9:446-51 pubmed publisher
    ..We show that EMCV IRES-initiated translation undergoes a CBP80/20-associated pioneer round of translation that results in CBP80/20-dependent and Upf factor-dependent NMD when translation terminates prematurely...
  37. Lu S, Cullen B. Nonsense mediated decay induced by tethered human UPF3B is restricted to the cytoplasm. RNA Biol. 2004;1:42-7 pubmed
    ..Recently, it has been demonstrated that RNA tethering of key mediators of NMD, including human UPF3B, accurately recreates NMD...
  38. Kashima I, Jonas S, Jayachandran U, Buchwald G, Conti E, Lupas A, et al. SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay. Genes Dev. 2010;24:2440-50 pubmed publisher
  39. Neu Yilik G, Raimondeau E, Eliseev B, Yeramala L, Amthor B, Deniaud A, et al. Dual function of UPF3B in early and late translation termination. EMBO J. 2017;36:2968-2986 pubmed publisher
    ..We discovered that UPF3B (i) interacts with the release factors, (ii) delays translation termination and (iii) dissociates post-termination ..
  40. Jones S, Wilkinson M. RNA decay, evolution, and the testis. RNA Biol. 2017;14:146-155 pubmed publisher
    ..We discuss the unusual evolution of UPF3A, whose paralog, UPF3B, has the opposite biochemical function and acts in brain development...
  41. Ma X, Yoon S, Richardson C, Jülich K, Blenis J. SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Cell. 2008;133:303-13 pubmed publisher
    ..Thus, SKAR-mediated recruitment of activated S6K1 to newly processed mRNPs serves as a conduit between mTOR checkpoint signaling and the pioneer round of translation when cells exist in conditions supportive of protein synthesis. ..
  42. Hackmann K, Rump A, Haas S, Lemke J, Fryns J, Tzschach A, et al. Tentative clinical diagnosis of Lujan-Fryns syndrome--A conglomeration of different genetic entities?. Am J Med Genet A. 2016;170A:94-102 pubmed publisher
    ..Mutations of three genes (MED12, UPF3B, and ZDHHC9) have been reported in "broadly defined" LFS...
  43. Ajamian L, Abel K, Rao S, Vyboh K, García de Gracia F, Soto Rifo R, et al. HIV-1 Recruits UPF1 but Excludes UPF2 to Promote Nucleocytoplasmic Export of the Genomic RNA. Biomolecules. 2015;5:2808-39 pubmed publisher
    ..we observed that both UPF2 and the long isoform of UPF3a, UPF3aL, but not the shorter isoforms UPF3aS and UPF3b, are excluded from the UPF1-Rev-CRM1-DDX3 complex as they are negative regulators of vRNA nuclear export...
  44. Yamashita A, Izumi N, Kashima I, Ohnishi T, Saari B, Katsuhata Y, et al. SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay. Genes Dev. 2009;23:1091-105 pubmed publisher
  45. Laumonnier F, Shoubridge C, Antar C, Nguyen L, Van Esch H, Kleefstra T, et al. Mutations of the UPF3B gene, which encodes a protein widely expressed in neurons, are associated with nonspecific mental retardation with or without autism. Mol Psychiatry. 2010;15:767-76 pubmed publisher
    Mutations in the UPF3B gene, which encodes a protein involved in nonsense-mediated mRNA decay, have recently been described in four families with specific (Lujan-Fryns and FG syndromes), nonspecific X-linked mental retardation (XLMR) and ..
  46. Alrahbeni T, Sartor F, Anderson J, Miedzybrodzka Z, McCaig C, Müller B. Full UPF3B function is critical for neuronal differentiation of neural stem cells. Mol Brain. 2015;8:33 pubmed publisher
    Mutation in the UPF3B gene on chromosome X is implicated in neurodevelopmental disorders including X-linked intellectual disability, autism and schizophrenia...
  47. Schell T, Kocher T, Wilm M, Seraphin B, Kulozik A, Hentze M. Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells. Biochem J. 2003;373:775-83 pubmed
    ..Components of the exon-exon junction complex or the translational eukaryotic release factor (eRF) 3 were not identified in complexes associated with Hupf1-2tag. We discuss these findings in the context of current models of NMD...
  48. Franks T, Singh G, Lykke Andersen J. Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay. Cell. 2010;143:938-50 pubmed publisher
    ..This uncovers a previously unappreciated and potentially regulated step in mRNA decay and raises the question of how other mRNA decay pathways release protein components of substrate mRNPs...
  49. Nguyen L, Jolly L, Shoubridge C, Chan W, Huang L, Laumonnier F, et al. Transcriptome profiling of UPF3B/NMD-deficient lymphoblastoid cells from patients with various forms of intellectual disability. Mol Psychiatry. 2012;17:1103-15 pubmed publisher
    ..In man, mutations in the NMD factor gene UPF3B, which disrupts a branch of the NMD pathway, cause various forms of intellectual disability (ID)...
  50. Lejeune F, Ranganathan A, Maquat L. eIF4G is required for the pioneer round of translation in mammalian cells. Nat Struct Mol Biol. 2004;11:992-1000 pubmed
    ..We propose a model in which eIF4G serves to connect CBP80/20 with other initiation factors during the pioneer round of translation. ..