SNRPD3

Summary

Gene Symbol: SNRPD3
Description: small nuclear ribonucleoprotein D3 polypeptide
Alias: SMD3, Sm-D3, small nuclear ribonucleoprotein Sm D3, small nuclear ribonucleoprotein D3 polypeptide 18kDa, snRNP core protein D3
Species: human
Products:     SNRPD3

Top Publications

  1. Kambach C, Walke S, Young R, Avis J, de La Fortelle E, Raker V, et al. Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell. 1999;96:375-87 pubmed
    ..The crystal structures suggest that the seven Sm proteins could form a closed ring and the snRNAs may be bound in the positively charged central hole. ..
  2. Liu Q, Fischer U, Wang F, Dreyfuss G. The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Cell. 1997;90:1013-21 pubmed
    ..These findings suggest a role for SMN and SIP1 in spliceosomal snRNP biogenesis and function and provide a likely molecular mechanism for the cause of SMA. ..
  3. Urlaub H, Raker V, Kostka S, Luhrmann R. Sm protein-Sm site RNA interactions within the inner ring of the spliceosomal snRNP core structure. EMBO J. 2001;20:187-96 pubmed
    ..Our results thus provide the first evidence that, within the core snRNP, multiple Sm protein-Sm site RNA contacts occur on the inner surface of the heptameric Sm protein ring. ..
  4. Charroux B, Pellizzoni L, Perkinson R, Shevchenko A, Mann M, Dreyfuss G. Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems. J Cell Biol. 1999;147:1181-94 pubmed
    ..Gemin3 interacts directly with SMN, as well as with SmB, SmD2, and SmD3. Immunolocalization studies using mAbs to Gemin3 show that it colocalizes with SMN in gems...
  5. Chari A, Golas M, Klingenhäger M, Neuenkirchen N, Sander B, Englbrecht C, et al. An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. Cell. 2008;135:497-509 pubmed publisher
    ..The mode of action of this combined chaperone/catalyst system is reminiscent of the mechanism employed by DNA clamp loaders. ..
  6. Friesen W, Wyce A, Paushkin S, Abel L, Rappsilber J, Mann M, et al. A novel WD repeat protein component of the methylosome binds Sm proteins. J Biol Chem. 2002;277:8243-7 pubmed
  7. Weber G, Trowitzsch S, Kastner B, Luhrmann R, Wahl M. Functional organization of the Sm core in the crystal structure of human U1 snRNP. EMBO J. 2010;29:4172-84 pubmed publisher
    ..The intricate, multi-layered interplay of proteins and RNA rationalizes the hierarchical assembly of U snRNPs in vitro and in vivo. ..
  8. Pomeranz Krummel D, Oubridge C, Leung A, Li J, Nagai K. Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution. Nature. 2009;458:475-80 pubmed publisher
    ..The structure of U1 snRNP provides insights into U1 snRNP assembly and suggests a possible mechanism of 5'-splice-site recognition. ..
  9. Meister G, Eggert C, Buhler D, Brahms H, Kambach C, Fischer U. Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln. Curr Biol. 2001;11:1990-4 pubmed
    ..Our data suggest that the pICln complex regulates an early step in the assembly of U snRNPs, possibly the transfer of Sm proteins to the SMN-complex. ..

More Information

Publications54

  1. Friesen W, Paushkin S, Wyce A, Massenet S, Pesiridis G, Van Duyne G, et al. The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins. Mol Cell Biol. 2001;21:8289-300 pubmed
    ..to the symmetrical dimethylarginine (sDMA)-modified arginine- and glycine-rich (RG-rich) domains of SmD1 and SmD3. We found that the unmodified, but not the sDMA-modified, RG domains of SmD1 and SmD3 associate with a 20S ..
  2. Brahms H, Raymackers J, Union A, De Keyser F, Meheus L, Luhrmann R. The C-terminal RG dipeptide repeats of the spliceosomal Sm proteins D1 and D3 contain symmetrical dimethylarginines, which form a major B-cell epitope for anti-Sm autoantibodies. J Biol Chem. 2000;275:17122-9 pubmed
  3. Miranda T, Khusial P, Cook J, Lee J, Gunderson S, Pestka S, et al. Spliceosome Sm proteins D1, D3, and B/B' are asymmetrically dimethylated at arginine residues in the nucleus. Biochem Biophys Res Commun. 2004;323:382-7 pubmed
    We report a novel modification of spliceosome proteins Sm D1, Sm D3, and Sm B/B'. L292 mouse fibroblasts were labeled in vivo with [3H]methionine...
  4. Lehmeier T, Raker V, Hermann H, Luhrmann R. cDNA cloning of the Sm proteins D2 and D3 from human small nuclear ribonucleoproteins: evidence for a direct D1-D2 interaction. Proc Natl Acad Sci U S A. 1994;91:12317-21 pubmed
    ..A., Manolson, M., Becherer, K., Weidenhammer, E., Kirkpatrick, D., Wright, R. & Jones, E. (1991) Mol. Cell. Biol. 11, 5801-5812], suggesting that this gene encodes the yeast homologue of the human D3 protein. ..
  5. Sleeman J, Lamond A. Newly assembled snRNPs associate with coiled bodies before speckles, suggesting a nuclear snRNP maturation pathway. Curr Biol. 1999;9:1065-74 pubmed
    ..These include speckles, coiled bodies and nucleoli, in addition to a diffuse nucleoplasmic compartment. The reasons for snRNP accumulation in these different structures are unclear...
  6. Friesen W, Massenet S, Paushkin S, Wyce A, Dreyfuss G. SMN, the product of the spinal muscular atrophy gene, binds preferentially to dimethylarginine-containing protein targets. Mol Cell. 2001;7:1111-7 pubmed
    ..SMN binds the arginine- and glycine-rich (RG) domains of the snRNP proteins SmD1 and SmD3. Specific arginines in these domains are modified to dimethylarginines, a common modification of unknown function...
  7. Flodrová D, Benkovská D, Macejova D, Bialešová L, Hunakova L, Brtko J, et al. Proteomic analysis of changes in the protein composition of MCF-7 human breast cancer cells induced by all-trans retinoic acid, 9-cis retinoic acid, and their combination. Toxicol Lett. 2015;232:226-32 pubmed publisher
    ..Heat shock protein 27, ribonucleoprotein SmD3, and cofilin-1 were significantly upregulated after treatment with combination of individual retinoic acid isomers...
  8. Zhu K, Song J, Tao H, Cheng Z, Jiang C, Zhang H. Discovery of new potent protein arginine methyltransferase 5 (PRMT5) inhibitors by assembly of key pharmacophores from known inhibitors. Bioorg Med Chem Lett. 2018;28:3693-3699 pubmed publisher
    ..arrest and apoptosis-inducing effects, as well as reduced the cellular symmetric arginine dimethylation level of SmD3 protein...
  9. Chan Penebre E, Kuplast K, Majer C, Boriack Sjodin P, Wigle T, Johnston L, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol. 2015;11:432-7 pubmed publisher
    ..Treatment of MCL cell lines with EPZ015666 led to inhibition of SmD3 methylation and cell death, with IC50 values in the nanomolar range...
  10. Zhu K, Tao H, Song J, Jin L, Zhang Y, Liu J, et al. Identification of 5-benzylidene-2-phenylthiazolones as potent PRMT5 inhibitors by virtual screening, structural optimization and biological evaluations. Bioorg Chem. 2018;81:289-298 pubmed publisher
    ..with EC50 values lower than 10 μM and reduced the cellular symmetric arginine dimethylation levels of SmD3 protein. Besides, 5 and 19 demonstrated the mechanism of cell killing in cell cycle arrest and apoptotic effect...
  11. Schwer B, Roth A, Shuman S. Will the circle be unbroken: specific mutations in the yeast Sm protein ring expose a requirement for assembly factor Brr1, a homolog of Gemin2. RNA. 2017;23:420-430 pubmed publisher
    ..264 pairwise combinations of SmD1 and SmD2 alleles with each other and with a collection of SmG, SmE, SmF, SmB, and SmD3 alleles revealed 92 instances of inter-Sm synthetic lethality...
  12. Gomez V, Wasserman M. Interactions between Giardia duodenalis Sm proteins and their association with spliceosomal snRNAs. Parasitol Res. 2017;116:617-626 pubmed publisher
    ..duodenalis. Haemagglutinin (HA)-tagged SmB and SmD3 proteins, which form part of the spliceosome core, were overexpressed in the parasite...
  13. Schwer B, Kruchten J, Shuman S. Structure-function analysis and genetic interactions of the SmG, SmE, and SmF subunits of the yeast Sm protein ring. RNA. 2016;22:1320-8 pubmed publisher
    ..interactions with non-Sm splicing factors showed that many benign mutations of SmG, SmE, and SmF (and of SmB and SmD3) were synthetically lethal with null alleles of U2 snRNP subunits Lea1 and Msl1...
  14. Zhang Y, Zhang J, Liu Z, Liu Y, Tuo S. A network-based approach to identify disease-associated gene modules through integrating DNA methylation and gene expression. Biochem Biophys Res Commun. 2015;465:437-42 pubmed publisher
    ..expression and methylation values of these genes between cases and controls, we find some genes, such as VASN, SNRPD3, and gene modules, targeted by POLR2C, CHMP1B and TAF9, which might be novel breast cancer-related biomarkers.
  15. Qiu X, Cheng J, Zhao J, Chang H, Leung P. Transforming growth factor-β stimulates human ovarian cancer cell migration by up-regulating connexin43 expression via Smad2/3 signaling. Cell Signal. 2015;27:1956-62 pubmed publisher
    ..In addition, siRNA-mediated knockdown of Smad2 or Smd3 abolishes TGF-β-induced up-regulation of Cx43 expression...
  16. Mao R, Shao J, Zhu K, Zhang Y, Ding H, Zhang C, et al. Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization. J Med Chem. 2017;60:6289-6304 pubmed publisher
    ..studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation...
  17. Li J, Leung A, Kondo Y, Oubridge C, Nagai K. Re-refinement of the spliceosomal U4 snRNP core-domain structure. Acta Crystallogr D Struct Biol. 2016;72:131-46 pubmed publisher
    ..The U4 Sm site-sequence AAUUUUU has been shown to bind to the seven Sm proteins SmF-SmE-SmG-SmD3-SmB-SmD1-SmD2 in an identical manner as the U1 Sm-site sequence AAUUUGU, except in SmD1 where the bound U replaces ..
  18. Handu M, Kaduskar B, Ravindranathan R, Soory A, Giri R, Elango V, et al. SUMO-Enriched Proteome for Drosophila Innate Immune Response. G3 (Bethesda). 2015;5:2137-54 pubmed publisher
    ..as cellular proteins with diverse functions, many being components of protein complexes, such as prosß4, Rps10b, SmD3, Tango7, and Aats-arg...
  19. Ehlers K, Clements R, Vermeer M, Giles J, Tran Q. Novel regulations of the angiotensin II receptor type 1 by calmodulin. Biochem Pharmacol. 2018;152:187-200 pubmed publisher
    ..a. 125-141), in addition to SMD3 and the juxtamembranous region of SMD4 (SMD4JM, a.a., 309-327)...
  20. Carissimi C, Baccon J, Straccia M, Chiarella P, Maiolica A, Sawyer A, et al. Unrip is a component of SMN complexes active in snRNP assembly. FEBS Lett. 2005;579:2348-54 pubmed
    ..These results demonstrate that unrip functions in the pathway of snRNP biogenesis and is a marker of cellular SMN complexes active in snRNP assembly. ..
  21. Weng M, Lee J, Wei S, Li Q, Shahamatdar S, Hsu D, et al. Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells. Proc Natl Acad Sci U S A. 2012;109:E3659-67 pubmed publisher
    ..ERH interacts with the spliceosome protein SNRPD3 and is required for the mRNA splicing of the mitotic motor protein CENP-E...
  22. Charroux B, Pellizzoni L, Perkinson R, Yong J, Shevchenko A, Mann M, et al. Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli. J Cell Biol. 2000;148:1177-86 pubmed
    ..Interestingly, Gemin4 is also detected in the nucleoli, suggesting that the SMN complex may also function in preribosomal RNA processing or ribosome assembly. ..
  23. Mahler M. Sm peptides in differentiation of autoimmune diseases. Adv Clin Chem. 2011;54:109-28 pubmed
    ..and BB' contain symmetrical dimethylarginine, constituting a major autoepitope within the C-terminus of SmD1 and SmD3. Several synthetic peptides have been used for the detection of anti-Sm antibodies and thus for the diagnosis of ..
  24. Friesen W, Dreyfuss G. Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN). J Biol Chem. 2000;275:26370-5 pubmed
    ..arginine- and glycine-rich domains comprising the last 29 amino acids of SmD1 and the last 32 amino acids of SmD3 are necessary and sufficient for SMN binding...
  25. Pillai R, Grimmler M, Meister G, Will C, Luhrmann R, Fischer U, et al. Unique Sm core structure of U7 snRNPs: assembly by a specialized SMN complex and the role of a new component, Lsm11, in histone RNA processing. Genes Dev. 2003;17:2321-33 pubmed
    ..Thus, the U7-specific Lsm11 protein not only specifies the assembly of the U7 Sm core but also fulfills an important role in U7 snRNP-mediated histone mRNA processing. ..
  26. Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G. Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex. J Biol Chem. 2002;277:31957-62 pubmed
    ..With the identification of Gemin7, the inventory of the core components of the SMN complex appears essentially complete. ..
  27. Gonsalvez G, Tian L, Ospina J, Boisvert F, Lamond A, Matera A. Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins. J Cell Biol. 2007;178:733-40 pubmed
    ..Furthermore, we show that the two enzymes function nonredundantly in Sm protein methylation. Lastly, we provide in vivo evidence demonstrating that Sm protein sDMA modification is required for snRNP biogenesis in human cells. ..
  28. Lehmeier T, Foulaki K, Luhrmann R. Evidence for three distinct D proteins, which react differentially with anti-Sm autoantibodies, in the cores of the major snRNPs U1, U2, U4/U6 and U5. Nucleic Acids Res. 1990;18:6475-84 pubmed
    ..Whether the additional band represents a distinct common snRNP protein or a post-translationally modified version of G is not yet known. ..
  29. Pesiridis G, Diamond E, Van Duyne G. Role of pICLn in methylation of Sm proteins by PRMT5. J Biol Chem. 2009;284:21347-59 pubmed publisher
    ..We find that pICln is a monomer in solution, binds with high affinity (K(d) approximately 160 nm) to SmD3-SmB, and forms 1:1 complexes with Sm proteins and Sm protein subcomplexes...
  30. Ma Y, Dostie J, Dreyfuss G, Van Duyne G. The Gemin6-Gemin7 heterodimer from the survival of motor neurons complex has an Sm protein-like structure. Structure. 2005;13:883-92 pubmed
  31. Pillai R, Will C, Luhrmann R, Schumperli D, Muller B. Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein. EMBO J. 2001;20:5470-9 pubmed
    ..This novel type of Sm complex, composed of both conventional Sm proteins and the Sm-like Lsm10, is most likely to be important for U7 snRNP function and subcellular localization. ..
  32. Leung A, Nagai K, Li J. Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis. Nature. 2011;473:536-9 pubmed publisher
    ..U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), contain seven Sm proteins (SmB/B', SmD1, SmD2, SmD3, SmE, SmF and SmG) in common...
  33. Yong J, Wan L, Dreyfuss G. Why do cells need an assembly machine for RNA-protein complexes?. Trends Cell Biol. 2004;14:226-32 pubmed
    ..We discuss how this surveillance capacity of the SMN complex might ensure assembly of Sm cores only on the correct RNAs and prevent illicit, potentially deleterious assembly of Sm cores on random RNAs. ..
  34. Gubitz A, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G. Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. J Biol Chem. 2002;277:5631-6 pubmed
    ..Furthermore, Gemin5 interacts with several of the snRNP core proteins including SmB, SmD1, SmD2, SmD3, and SmE, suggesting that it participates in the activities of the SMN complex in snRNP assembly...
  35. Pellizzoni L, Baccon J, Rappsilber J, Mann M, Dreyfuss G. Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component. J Biol Chem. 2002;277:7540-5 pubmed
    ..Co-immunoprecipitation, immunolocalization, and in vitro binding experiments demonstrate that Gemin6 is a component of the SMN complex that localizes to gems and interacts with several Sm proteins of the spliceosomal snRNPs. ..
  36. Fronz K, Otto S, Kölbel K, Kuhn U, Friedrich H, Schierhorn A, et al. Promiscuous modification of the nuclear poly(A)-binding protein by multiple protein-arginine methyltransferases does not affect the aggregation behavior. J Biol Chem. 2008;283:20408-20 pubmed publisher
    ..Thus, arginine methylation might be relevant for oculopharyngeal muscular dystrophy. However, in two different types of assays we have been unable to detect any effect of arginine methylation on the aggregation of bovine PABPN1. ..
  37. Fong Y, Zhou Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature. 2001;414:929-33 pubmed
    ..Because the TAT-SF1-U snRNP complex also stimulates splicing in vitro, it may serve as a dual-function factor to couple transcription and splicing and to facilitate their reciprocal activation. ..
  38. Fury M, Zhang W, Christodoulopoulos I, Zieve G. Multiple protein: protein interactions between the snRNP common core proteins. Exp Cell Res. 1997;237:63-9 pubmed
    ..Other interactions were between proteins in the 6S and 20S particles or within the 20S particle itself. These interactions are likely to occur within the cytoplasmic snRNP core protein complexes and the mature snRNP particle. ..
  39. Fu D, Collins K. Purification of human telomerase complexes identifies factors involved in telomerase biogenesis and telomere length regulation. Mol Cell. 2007;28:773-85 pubmed
  40. Khusial P, Vaidya K, Zieve G. The symmetrical dimethylarginine post-translational modification of the SmD3 protein is not required for snRNP assembly and nuclear transport. Biochem Biophys Res Commun. 2005;337:1119-24 pubmed
    The SmB, SmD1, and SmD3 proteins have the rare symmetrical dimethylarginine post-translational modification in their C-termini...
  41. Girard C, Mouaikel J, Neel H, Bertrand E, Bordonné R. Nuclear localization properties of a conserved protuberance in the Sm core complex. Exp Cell Res. 2004;299:199-208 pubmed
    ..immunolocalization as well as biochemical experiments, we show here that the C-terminal domains of human SmD1 and SmD3 proteins possess nuclear localization properties...
  42. Buhler D, Raker V, Luhrmann R, Fischer U. Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly: implications for spinal muscular atrophy. Hum Mol Genet. 1999;8:2351-7 pubmed
    ..Thus, our data show that SMN is an essential U snRNP assembly factor and establish a direct correlation between defects in the biogenesis of U snRNPs and SMA. ..
  43. Gomez V, Wasserman M. Partial inhibition of two genes that encode spliceosomal proteins in Giardia intestinalis. Biomedica. 2016;36:128-36 pubmed publisher
    ..Materials and methods. Antisense sequences of the genes encoding the spliceosomal parasite proteins SmB and SmD3 were cloned into a specific G. intestinalis vector. G...
  44. Mahler M, Stinton L, Fritzler M. Improved serological differentiation between systemic lupus erythematosus and mixed connective tissue disease by use of an SmD3 peptide-based immunoassay. Clin Diagn Lab Immunol. 2005;12:107-13 pubmed
    ..Diagnostics), 10 and 94%, respectively, for the QuantaPlex Sm (INOVA), and 12 and 100%, respectively, for the new SmD3 peptide-based ELISA (Varelisa Sm Antibodies)...
  45. Mahler M, Fritzler M, Bluthner M. Identification of a SmD3 epitope with a single symmetrical dimethylation of an arginine residue as a specific target of a subpopulation of anti-Sm antibodies. Arthritis Res Ther. 2005;7:R19-29 pubmed
    ..we confirmed that the dimethylated arginine residues play an essential role in the formation of major SmD1 and SmD3 autoepitopes...