The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

LSM2  -  LSM2 homolog, U6 small nuclear RNA...

Homo sapiens

Synonyms: C6orf28, G7B, G7b, Protein G7b, Small nuclear ribonuclear protein D homolog, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of LSM2


High impact information on LSM2

  • The upstream cleavage product corresponds to the mature histone mRNA, while the downstream product is degraded by a 5'-3' exonuclease, also dependent on the U7 snRNP [6].
  • On the basis of this analysis, we describe a new type of U1 snRNP binding site in an intron that is essential for accurate intron removal [7].
  • The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis [8].
  • Defects in spliceosomal snRNP biogenesis may, therefore, be the cause of SMA [8].
  • The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins [9].

Chemical compound and disease context of LSM2


Biological context of LSM2

  • Together with previous results, these data indicate that methylation of Sm proteins by the methylosome directs Sm proteins to the SMN complex for assembly into snRNP core particles and suggest that the methylosome can regulate snRNP assembly [12].
  • LSM 2 demonstrated the best combination of low bias [0.1% (-8.9%, 11%) and 11% (4.3%, 15%)] and high accuracy [-1.0% (-12%, 24%) and 14% (7.9%, 37%)] for temozolomide clearance and MTIC AUC, respectively [13].
  • The human U1 snRNP-specific U1A protein inhibits polyadenylation of its own pre-mRNA [14].
  • Oligonucleotide directed RNAase H degradation indicates that this 5' end region is available for base pairing interactions within the HSUR 1 and HSUR 2 snRNP particles [15].
  • A short RNA oligonucleotide comprising the 5' splice site consensus sequence (5'SS RNA) is sufficient to bind U1 small nuclear ribonucleoprotein particle (snRNP) or to induce the association of U2 snRNP and U4-U5-U6 triple snRNP [16].

Anatomical context of LSM2

  • Entry of U2 snRNP into the spliceosome is initiated by interaction of the essential splicing factor U2AF65 with the pre-mRNA polypyrimidine tract [17].
  • The survival motor neuron (SMN) protein, the spinal muscular atrophy disease gene product, is crucial for snRNP core particle assembly in vivo [12].
  • Analysis of the mature rRNAs and rRNA intermediates that accumulate in the U8-depleted oocytes indicate that the U8 snRNP is essential for correct maturation of the 5.8S and 28S rRNAs at both their 5' and 3' ends [18].
  • cDNA encoding a 70 kd protein (70K) associated with U1 small nuclear ribonucleoprotein (snRNP) was cloned from a human brain-stem library using autoantibodies from patients with connective tissue disease [19].
  • In eukaryotic cells, the conversion of gene transcripts into messenger RNA's involves multiple factors, including the highly abundant small nuclear ribonucleoprotein (snRNP) complexes that mediate the splicing reaction [20].

Associations of LSM2 with chemical compounds

  • The methylosome functions to modify specific arginines to dimethylarginines in the arginine- and glycine-rich domains of several spliceosomal Sm proteins, and this modification targets these proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein (snRNP) core particles [21].
  • Results from Monte-Carlo simulations also revealed that LSM 2 had the best combination of lowest bias (0.1+/-6.1% and -0.8+/-6.5%), and the highest accuracy (4.5+/-4.1% and 5.0+/-4.3%) for temozolomide clearance and MTIC apparent clearance, respectively [13].
  • These antibodies were used to immunoprecipitate sucrose gradient fractionated pulse-labeled and pulse/chased snRNP proteins [2].
  • A factor, U2AF, is required for U2 snRNP binding and splicing complex assembly [22].
  • We have used antisense 2'-OMe RNA oligonucleotides carrying four 5'-terminal biotin residues to probe the structure and function of the human U4/U6 snRNP [23].

Physical interactions of LSM2

  • SMN oligomers interact avidly with the snRNP core proteins SmB, -D1, and -D3 [1].
  • Mutations in the polypyrimidine tract that reduce the binding of pPTB also reduce the efficiency of formation of the pre-spliceosome complex containing U2 snRNP [24].
  • This implies that the PRMT5 complex is involved in an early stage of U7 snRNP assembly and hence may have a second snRNP assembly function unrelated to sDMA modification [25].
  • We previously identified a 100-kDa zinc finger protein (ZFP100) as a component of U7 snRNP that interacts with the SLBP/pre-mRNA complex [26].
  • The data indicate that SPF30 is an essential human splicing factor that may act to dock the U4/U5/U6 tri-snRNP to the A complex during spliceosome assembly or, alternatively, may act as a late assembly factor in both the tri-snRNP and the A-complex [27].

Enzymatic interactions of LSM2


Regulatory relationships of LSM2

  • SLBP binds histone pre-mRNAs and facilitates 3'-end processing by promoting stable association of U7 snRNP with the pre-mRNA [30].
  • The polypyrimidine tract binding protein (PTB) promotes exon skipping by binding to an exonic splicing silencer and inhibiting the association of U2AF and U2 snRNP with the upstream 3' splice site, without affecting recognition of the downstream 5' splice site by U1 [31].
  • Furthermore, in vitro phosphorylation of TIA-1 by FAST K results in enhanced U1 snRNP recruitment [32].
  • These and related data support the view that the poly-TPR Clf1p splicing factor promotes the functional integration of the U4/U6.U5 tri-snRNP particle into the U1-, U2-dependent prespliceosome [33].
  • snRNP protein expression enhances the formation of Cajal bodies containing p80-coilin and SMN [34].

Other interactions of LSM2

  • This suggests that SMN also functions in the assembly of the U6 snRNP in the nucleus and in the assembly of other Lsm-containing complexes [1].
  • Our results reveal a new function of U2AF65: to position a DEAD box protein required for U2 snRNP binding at the pre-mRNA branchpoint region [17].
  • The human 56-kD U2AF(65)-associated protein (hUAP56), a member of the DExD/H box protein family of RNA-dependent ATPases, is required for the stable binding of U2 snRNP to the pre-mRNA branchpoint [35].
  • The SMN protein is tightly associated with a novel protein, SIP1, and together they form a complex with several spliceosomal snRNP proteins [8].
  • It is likely that the RBD of SLBP interacts directly with both the stem-loop RNA and other processing factor(s), most likely the U7 snRNP, to facilitate histone pre-mRNA processing [36].

Analytical, diagnostic and therapeutic context of LSM2


  1. Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN). Friesen, W.J., Dreyfuss, G. J. Biol. Chem. (2000) [Pubmed]
  2. Small nuclear ribonucleoprotein particle assembly in vivo: demonstration of a 6S RNA-free core precursor and posttranslational modification. Fisher, D.E., Conner, G.E., Reeves, W.H., Wisniewolski, R., Blobel, G. Cell (1985) [Pubmed]
  3. Reduced U snRNP assembly causes motor axon degeneration in an animal model for spinal muscular atrophy. Winkler, C., Eggert, C., Gradl, D., Meister, G., Giegerich, M., Wedlich, D., Laggerbauer, B., Fischer, U. Genes Dev. (2005) [Pubmed]
  4. Human anti-p68 autoantibodies recognize a common epitope of U1 RNA containing small nuclear ribonucleoprotein and influenza B virus. Guldner, H.H., Netter, H.J., Szostecki, C., Jaeger, E., Will, H. J. Exp. Med. (1990) [Pubmed]
  5. Antifibrillarin autoantibodies present in systemic sclerosis and other connective tissue diseases interact with similar epitopes. Kasturi, K.N., Hatakeyama, A., Spiera, H., Bona, C.A. J. Exp. Med. (1995) [Pubmed]
  6. The polyadenylation factor CPSF-73 is involved in histone-pre-mRNA processing. Dominski, Z., Yang, X.C., Marzluff, W.F. Cell (2005) [Pubmed]
  7. A new type of mutation causes a splicing defect in ATM. Pagani, F., Buratti, E., Stuani, C., Bendix, R., Dörk, T., Baralle, F.E. Nat. Genet. (2002) [Pubmed]
  8. The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Fischer, U., Liu, Q., Dreyfuss, G. Cell (1997) [Pubmed]
  9. The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Liu, Q., Fischer, U., Wang, F., Dreyfuss, G. Cell (1997) [Pubmed]
  10. Human T cell clones reactive against U-small nuclear ribonucleoprotein autoantigens from connective tissue disease patients and healthy individuals. Hoffman, R.W., Takeda, Y., Sharp, G.C., Lee, D.R., Hill, D.L., Kaneoka, H., Caldwell, C.W. J. Immunol. (1993) [Pubmed]
  11. Autoimmune disease antigen U1 snRNP neutralizes heparin. Scully, M.F., Gebska, M.A. J. Thromb. Haemost. (2003) [Pubmed]
  12. The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins. Friesen, W.J., Paushkin, S., Wyce, A., Massenet, S., Pesiridis, G.S., Van Duyne, G., Rappsilber, J., Mann, M., Dreyfuss, G. Mol. Cell. Biol. (2001) [Pubmed]
  13. Development of a pharmacokinetic limited sampling model for temozolomide and its active metabolite MTIC. Kirstein, M.N., Panetta, J.C., Gajjar, A., Nair, G., Iacono, L.C., Freeman, B.B., Stewart, C.F. Cancer Chemother. Pharmacol. (2005) [Pubmed]
  14. The human U1 snRNP-specific U1A protein inhibits polyadenylation of its own pre-mRNA. Boelens, W.C., Jansen, E.J., van Venrooij, W.J., Stripecke, R., Mattaj, I.W., Gunderson, S.I. Cell (1993) [Pubmed]
  15. Four novel U RNAs are encoded by a herpesvirus. Lee, S.I., Murthy, S.C., Trimble, J.J., Desrosiers, R.C., Steitz, J.A. Cell (1988) [Pubmed]
  16. Disruption of base pairing between the 5' splice site and the 5' end of U1 snRNA is required for spliceosome assembly. Konforti, B.B., Koziolkiewicz, M.J., Konarska, M.M. Cell (1993) [Pubmed]
  17. U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Fleckner, J., Zhang, M., Valcárcel, J., Green, M.R. Genes Dev. (1997) [Pubmed]
  18. Disruption of U8 nucleolar snRNA inhibits 5.8S and 28S rRNA processing in the Xenopus oocyte. Peculis, B.A., Steitz, J.A. Cell (1993) [Pubmed]
  19. A human autoimmune protein associated with U1 RNA contains a region of homology that is cross-reactive with retroviral p30gag antigen. Query, C.C., Keene, J.D. Cell (1987) [Pubmed]
  20. Identification of the human U7 snRNP as one of several factors involved in the 3' end maturation of histone premessenger RNA's. Mowry, K.L., Steitz, J.A. Science (1987) [Pubmed]
  21. A novel WD repeat protein component of the methylosome binds Sm proteins. Friesen, W.J., Wyce, A., Paushkin, S., Abel, L., Rappsilber, J., Mann, M., Dreyfuss, G. J. Biol. Chem. (2002) [Pubmed]
  22. A factor, U2AF, is required for U2 snRNP binding and splicing complex assembly. Ruskin, B., Zamore, P.D., Green, M.R. Cell (1988) [Pubmed]
  23. Antisense probing of the human U4/U6 snRNP with biotinylated 2'-OMe RNA oligonucleotides. Blencowe, B.J., Sproat, B.S., Ryder, U., Barabino, S., Lamond, A.I. Cell (1989) [Pubmed]
  24. Characterization of cDNAs encoding the polypyrimidine tract-binding protein. Gil, A., Sharp, P.A., Jamison, S.F., Garcia-Blanco, M.A. Genes Dev. (1991) [Pubmed]
  25. Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm proteins with PRMT5 and SMN complexes. Azzouz, T.N., Pillai, R.S., Däpp, C., Chari, A., Meister, G., Kambach, C., Fischer, U., Schümperli, D. J. Biol. Chem. (2005) [Pubmed]
  26. Conserved zinc fingers mediate multiple functions of ZFP100, a U7snRNP associated protein. Wagner, E.J., Ospina, J.K., Hu, Y., Dundr, M., Matera, A.G., Marzluff, W.F. RNA (2006) [Pubmed]
  27. SPF30 is an essential human splicing factor required for assembly of the U4/U5/U6 tri-small nuclear ribonucleoprotein into the spliceosome. Rappsilber, J., Ajuh, P., Lamond, A.I., Mann, M. J. Biol. Chem. (2001) [Pubmed]
  28. The [U4/U6.U5] tri-snRNP-specific 27K protein is a novel SR protein that can be phosphorylated by the snRNP-associated protein kinase. Fetzer, S., Lauber, J., Will, C.L., Lührmann, R. RNA (1997) [Pubmed]
  29. Deficient brain snRNP70K in patients with Down syndrome. Seidl, R., Labudova, O., Krapfenbauer, K., Henriksson, E.W., Craft, J., Turhani-Schatzmann, D., Achsel, T., Bidmon, B., Pruijn, G.J., Cairns, N., Lubec, G. Electrophoresis (2001) [Pubmed]
  30. A novel zinc finger protein is associated with U7 snRNP and interacts with the stem-loop binding protein in the histone pre-mRNP to stimulate 3'-end processing. Dominski, Z., Erkmann, J.A., Yang, X., Sànchez, R., Marzluff, W.F. Genes Dev. (2002) [Pubmed]
  31. Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition. Izquierdo, J.M., Majós, N., Bonnal, S., Martínez, C., Castelo, R., Guigó, R., Bilbao, D., Valcárcel, J. Mol. Cell (2005) [Pubmed]
  32. Fas-activated serine/threonine kinase (FAST K) synergizes with TIA-1/TIAR proteins to regulate Fas alternative splicing. Izquierdo, J.M., Valcárcel, J. J. Biol. Chem. (2007) [Pubmed]
  33. The Clf1p splicing factor promotes spliceosome assembly through N-terminal tetratricopeptide repeat contacts. Wang, Q., Hobbs, K., Lynn, B., Rymond, B.C. J. Biol. Chem. (2003) [Pubmed]
  34. snRNP protein expression enhances the formation of Cajal bodies containing p80-coilin and SMN. Sleeman, J.E., Ajuh, P., Lamond, A.I. J. Cell. Sci. (2001) [Pubmed]
  35. Identification and characterization of yUAP/Sub2p, a yeast homolog of the essential human pre-mRNA splicing factor hUAP56. Zhang, M., Green, M.R. Genes Dev. (2001) [Pubmed]
  36. Mutations in the RNA binding domain of stem-loop binding protein define separable requirements for RNA binding and for histone pre-mRNA processing. Dominski, Z., Erkmann, J.A., Greenland, J.A., Marzluff, W.F. Mol. Cell. Biol. (2001) [Pubmed]
  37. 3' cleavage and polyadenylation of mRNA precursors in vitro requires a poly(A) polymerase, a cleavage factor, and a snRNP. Christofori, G., Keller, W. Cell (1988) [Pubmed]
  38. Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle. Stark, H., Dube, P., Lührmann, R., Kastner, B. Nature (2001) [Pubmed]
  39. Nucleoplasmic organization of small nuclear ribonucleoproteins in cultured human cells. Matera, A.G., Ward, D.C. J. Cell Biol. (1993) [Pubmed]
  40. Combined biochemical and electron microscopic analyses reveal the architecture of the mammalian U2 snRNP. Krämer, A., Grüter, P., Gröning, K., Kastner, B. J. Cell Biol. (1999) [Pubmed]
WikiGenes - Universities