4v98

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The 8S snRNP Assembly IntermediateThe 8S snRNP Assembly Intermediate

Structural highlights

4v98 is a 160 chain structure with sequence from Drome and Human. This structure supersedes the now removed PDB entries 1vu2, 1vu3 and 4f77. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:SNRPD1 (HUMAN), SNRPD2 (HUMAN), SNRPE (HUMAN), SNRPF, PBSCF (HUMAN), Smn, CG16725, Dmel_CG16725 (DROME), Gem2, CG10419, Dmel_CG10419 (DROME), Dmel_CG4924, icln, icln-RA (DROME), SNRPG, PBSCG (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GEMI2_DROME] The SMN complex plays an essential role in spliceosomal snRNP assembly in the cytoplasm, is required for pre-mRNA splicing in the nucleus and acts as a chaperone that discriminates target and non-target RNAs of Sm proteins.[1] [2] [RUXE_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [ICLN_DROME] Chaperone that regulates the assembly of spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus (By similarity). [SMD2_HUMAN] Required for pre-mRNA splicing. Required for snRNP biogenesis (By similarity). [RUXG_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [SMD1_HUMAN] May act as a charged protein scaffold to promote snRNP assembly or strengthen snRNP-snRNP interactions through nonspecific electrostatic contacts with RNA. [RUXF_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [SMN_DROME] The SMN complex plays an essential role in spliceosomal snRNP assembly in the cytoplasm, is required for pre-mRNA splicing in the nucleus and acts as a chaperone that discriminates target and non-target RNAs of Sm proteins. Required for normal expression of spliceosomal snRNAs and for U12 intron splicing. Required in cholinergic neurons, but not in motor neurons, to ensure correct splicing and proper levels of stas mRNA and normal neurotransmitter release by motor neurons (PubMed:23063130 and PubMed:23063131). However, Smn is required in motor neurons, but not in cholinergic neurons, for normal motor behavior but plays no role in synaptic transmission according to PubMed:23103409. In both muscle and neurons, required for the formation of a normal neuromuscular junction (NMJ) structure. Plays a neuron-specific role in long-term homeostatic compensation at the larval NMJ. In the thorax of adult flies, required for Act88F, an indirect flight muscle (IFM)-specific actin, expression and for proper IFM myofibril formation. In nurse cells, oocytes and follicle cells, required to maintain normal organization of nuclear compartments including chromosomes, nucleoli, Cajal bodies, histone locus bodies and heterochromatin. Required for the functional integrity of the cytoplasmic U snRNP body (U body) and P body. Required in dividing postembryonic neuroblasts (pNBs) for the correct basal localization of mira. The tight regulation of its expression is critical for stem cell division, proliferation and differentiation in male germline and developing central nervous system (CNS). Required for tracheal terminal cell lumen formation.[3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]

Publication Abstract from PubMed

Small nuclear ribonucleoproteins (snRNPs) represent key constituents of major and minor spliceosomes. snRNPs contain a common core, composed of seven Sm proteins bound to snRNA, which forms in a step-wise and factor-mediated reaction. The assembly chaperone pICln initially mediates the formation of an otherwise unstable pentameric Sm protein unit. This so-called 6S complex docks subsequently onto the SMN complex, which removes pICln and enables the transfer of pre-assembled Sm proteins onto snRNA. X-ray crystallography and electron microscopy was used to investigate the structural basis of snRNP assembly. The 6S complex structure identifies pICln as an Sm protein mimic, which enables the topological organization of the Sm pentamer in a closed ring. A second structure of 6S bound to the SMN complex components SMN and Gemin2 uncovers a plausible mechanism of pICln elimination and Sm protein activation for snRNA binding. Our studies reveal how assembly factors facilitate formation of RNA-protein complexes in vivo.

Structural Basis of Assembly Chaperone- Mediated snRNP Formation.,Grimm C, Chari A, Pelz JP, Kuper J, Kisker C, Diederichs K, Stark H, Schindelin H, Fischer U Mol Cell. 2013 Jan 15. pii: S1097-2765(12)01018-0. doi:, 10.1016/j.molcel.2012.12.009. PMID:23333303[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Kroiss M, Schultz J, Wiesner J, Chari A, Sickmann A, Fischer U. Evolution of an RNP assembly system: a minimal SMN complex facilitates formation of UsnRNPs in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10045-50. doi:, 10.1073/pnas.0802287105. Epub 2008 Jul 10. PMID:18621711 doi:http://dx.doi.org/10.1073/pnas.0802287105
  2. ↑ Grimm C, Chari A, Pelz JP, Kuper J, Kisker C, Diederichs K, Stark H, Schindelin H, Fischer U. Structural Basis of Assembly Chaperone- Mediated snRNP Formation. Mol Cell. 2013 Jan 15. pii: S1097-2765(12)01018-0. doi:, 10.1016/j.molcel.2012.12.009. PMID:23333303 doi:http://dx.doi.org/10.1016/j.molcel.2012.12.009
  3. ↑ Chan YB, Miguel-Aliaga I, Franks C, Thomas N, Trulzsch B, Sattelle DB, Davies KE, van den Heuvel M. Neuromuscular defects in a Drosophila survival motor neuron gene mutant. Hum Mol Genet. 2003 Jun 15;12(12):1367-76. PMID:12783845
  4. ↑ Rajendra TK, Gonsalvez GB, Walker MP, Shpargel KB, Salz HK, Matera AG. A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle. J Cell Biol. 2007 Mar 12;176(6):831-41. PMID:17353360 doi:http://dx.doi.org/10.1083/jcb.200610053
  5. ↑ Kroiss M, Schultz J, Wiesner J, Chari A, Sickmann A, Fischer U. Evolution of an RNP assembly system: a minimal SMN complex facilitates formation of UsnRNPs in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10045-50. doi:, 10.1073/pnas.0802287105. Epub 2008 Jul 10. PMID:18621711 doi:http://dx.doi.org/10.1073/pnas.0802287105
  6. ↑ Chang HC, Dimlich DN, Yokokura T, Mukherjee A, Kankel MW, Sen A, Sridhar V, Fulga TA, Hart AC, Van Vactor D, Artavanis-Tsakonas S. Modeling spinal muscular atrophy in Drosophila. PLoS One. 2008 Sep 15;3(9):e3209. doi: 10.1371/journal.pone.0003209. PMID:18791638 doi:http://dx.doi.org/10.1371/journal.pone.0003209
  7. ↑ Lee L, Davies SE, Liu JL. The spinal muscular atrophy protein SMN affects Drosophila germline nuclear organization through the U body-P body pathway. Dev Biol. 2009 Aug 1;332(1):142-55. doi: 10.1016/j.ydbio.2009.05.553. Epub 2009, May 21. PMID:19464282 doi:http://dx.doi.org/10.1016/j.ydbio.2009.05.553
  8. ↑ Grice SJ, Liu JL. Survival motor neuron protein regulates stem cell division, proliferation, and differentiation in Drosophila. PLoS Genet. 2011 Apr;7(4):e1002030. doi: 10.1371/journal.pgen.1002030. Epub 2011 , Apr 7. PMID:21490958 doi:http://dx.doi.org/10.1371/journal.pgen.1002030
  9. ↑ Praveen K, Wen Y, Matera AG. A Drosophila model of spinal muscular atrophy uncouples snRNP biogenesis functions of survival motor neuron from locomotion and viability defects. Cell Rep. 2012 Jun 28;1(6):624-31. doi: 10.1016/j.celrep.2012.05.014. Epub 2012, Jun 21. PMID:22813737 doi:http://dx.doi.org/10.1016/j.celrep.2012.05.014
  10. ↑ Ruiz OE, Nikolova LS, Metzstein MM. Drosophila Zpr1 (Zinc finger protein 1) is required downstream of both EGFR and FGFR signaling in tracheal subcellular lumen formation. PLoS One. 2012;7(9):e45649. doi: 10.1371/journal.pone.0045649. Epub 2012 Sep 18. PMID:23029159 doi:http://dx.doi.org/10.1371/journal.pone.0045649
  11. ↑ Imlach WL, Beck ES, Choi BJ, Lotti F, Pellizzoni L, McCabe BD. SMN is required for sensory-motor circuit function in Drosophila. Cell. 2012 Oct 12;151(2):427-39. doi: 10.1016/j.cell.2012.09.011. PMID:23063130 doi:http://dx.doi.org/10.1016/j.cell.2012.09.011
  12. ↑ Lotti F, Imlach WL, Saieva L, Beck ES, Hao le T, Li DK, Jiao W, Mentis GZ, Beattie CE, McCabe BD, Pellizzoni L. An SMN-dependent U12 splicing event essential for motor circuit function. Cell. 2012 Oct 12;151(2):440-54. doi: 10.1016/j.cell.2012.09.012. PMID:23063131 doi:http://dx.doi.org/10.1016/j.cell.2012.09.012
  13. ↑ Timmerman C, Sanyal S. Behavioral and electrophysiological outcomes of tissue-specific Smn knockdown in Drosophila melanogaster. Brain Res. 2012 Dec 13;1489:66-80. doi: 10.1016/j.brainres.2012.10.035. Epub 2012, Oct 26. PMID:23103409 doi:http://dx.doi.org/10.1016/j.brainres.2012.10.035
  14. ↑ Grimm C, Chari A, Pelz JP, Kuper J, Kisker C, Diederichs K, Stark H, Schindelin H, Fischer U. Structural Basis of Assembly Chaperone- Mediated snRNP Formation. Mol Cell. 2013 Jan 15. pii: S1097-2765(12)01018-0. doi:, 10.1016/j.molcel.2012.12.009. PMID:23333303 doi:http://dx.doi.org/10.1016/j.molcel.2012.12.009
  15. ↑ Grimm C, Chari A, Pelz JP, Kuper J, Kisker C, Diederichs K, Stark H, Schindelin H, Fischer U. Structural Basis of Assembly Chaperone- Mediated snRNP Formation. Mol Cell. 2013 Jan 15. pii: S1097-2765(12)01018-0. doi:, 10.1016/j.molcel.2012.12.009. PMID:23333303 doi:http://dx.doi.org/10.1016/j.molcel.2012.12.009

4v98, resolution 3.10Å

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