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Structural Insights into Nuclear pre-mRNA Splicing in Higher Eukaryotes.

Kastner B, Will CL, Stark H, Lührmann R.

Cold Spring Harb Perspect Biol. 2019 Feb 14. pii: a032417. doi: 10.1101/cshperspect.a032417. [Epub ahead of print]


Multiple RNA-RNA tertiary interactions are dispensable for formation of a functional U2/U6 RNA catalytic core in the spliceosome.

Bao P, Boon KL, Will CL, Hartmuth K, Lührmann R.

Nucleic Acids Res. 2018 Dec 14;46(22):12126-12138. doi: 10.1093/nar/gky966.


Structural Basis of Splicing Modulation by Antitumor Macrolide Compounds.

Cretu C, Agrawal AA, Cook A, Will CL, Fekkes P, Smith PG, Lührmann R, Larsen N, Buonamici S, Pena V.

Mol Cell. 2018 Apr 19;70(2):265-273.e8. doi: 10.1016/j.molcel.2018.03.011. Epub 2018 Apr 12.


The Sm-core mediates the retention of partially-assembled spliceosomal snRNPs in Cajal bodies until their full maturation.

Roithová A, Klimešová K, Pánek J, Will CL, Lührmann R, Stanek D, Girard C.

Nucleic Acids Res. 2018 Apr 20;46(7):3774-3790. doi: 10.1093/nar/gky070.


The RES complex is required for efficient transformation of the precatalytic B spliceosome into an activated Bact complex.

Bao P, Will CL, Urlaub H, Boon KL, Lührmann R.

Genes Dev. 2017 Dec 1;31(23-24):2416-2429. doi: 10.1101/gad.308163.117. Epub 2018 Jan 12.


Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation.

Bertram K, Agafonov DE, Dybkov O, Haselbach D, Leelaram MN, Will CL, Urlaub H, Kastner B, Lührmann R, Stark H.

Cell. 2017 Aug 10;170(4):701-713.e11. doi: 10.1016/j.cell.2017.07.011. Epub 2017 Aug 3.


SUMO conjugation to spliceosomal proteins is required for efficient pre-mRNA splicing.

Pozzi B, Bragado L, Will CL, Mammi P, Risso G, Urlaub H, Lührmann R, Srebrow A.

Nucleic Acids Res. 2017 Jun 20;45(11):6729-6745. doi: 10.1093/nar/gkx213.


Identification of a small molecule inhibitor that stalls splicing at an early step of spliceosome activation.

Sidarovich A, Will CL, Anokhina MM, Ceballos J, Sievers S, Agafonov DE, Samatov T, Bao P, Kastner B, Urlaub H, Waldmann H, Lührmann R.

Elife. 2017 Mar 16;6. pii: e23533. doi: 10.7554/eLife.23533.


Cryo-EM structure of a human spliceosome activated for step 2 of splicing.

Bertram K, Agafonov DE, Liu WT, Dybkov O, Will CL, Hartmuth K, Urlaub H, Kastner B, Stark H, Lührmann R.

Nature. 2017 Feb 16;542(7641):318-323. doi: 10.1038/nature21079. Epub 2017 Jan 11.


Molecular Architecture of SF3b and Structural Consequences of Its Cancer-Related Mutations.

Cretu C, Schmitzová J, Ponce-Salvatierra A, Dybkov O, De Laurentiis EI, Sharma K, Will CL, Urlaub H, Lührmann R, Pena V.

Mol Cell. 2016 Oct 20;64(2):307-319. doi: 10.1016/j.molcel.2016.08.036. Epub 2016 Oct 6.


Rational Design of Cyclic Peptide Inhibitors of U2AF Homology Motif (UHM) Domains To Modulate Pre-mRNA Splicing.

Jagtap PK, Garg D, Kapp TG, Will CL, Demmer O, Lührmann R, Kessler H, Sattler M.

J Med Chem. 2016 Nov 23;59(22):10190-10197. Epub 2016 Nov 4.


U6atac snRNA stem-loop interacts with U12 p65 RNA binding protein and is functionally interchangeable with the U12 apical stem-loop III.

Singh J, Sikand K, Conrad H, Will CL, Komar AA, Shukla GC.

Sci Rep. 2016 Aug 11;6:31393. doi: 10.1038/srep31393.


ATPγS stalls splicing after B complex formation but prior to spliceosome activation.

Agafonov DE, van Santen M, Kastner B, Dube P, Will CL, Urlaub H, Lührmann R.

RNA. 2016 Sep;22(9):1329-37. doi: 10.1261/rna.057810.116. Epub 2016 Jul 13.


A spliceosome intermediate with loosely associated tri-snRNP accumulates in the absence of Prp28 ATPase activity.

Boesler C, Rigo N, Anokhina MM, Tauchert MJ, Agafonov DE, Kastner B, Urlaub H, Ficner R, Will CL, Lührmann R.

Nat Commun. 2016 Jul 5;7:11997. doi: 10.1038/ncomms11997.


Multiple protein-protein interactions converging on the Prp38 protein during activation of the human spliceosome.

Schütze T, Ulrich AK, Apelt L, Will CL, Bartlick N, Seeger M, Weber G, Lührmann R, Stelzl U, Wahl MC.

RNA. 2016 Feb;22(2):265-77. doi: 10.1261/rna.054296.115. Epub 2015 Dec 16.


Stable tri-snRNP integration is accompanied by a major structural rearrangement of the spliceosome that is dependent on Prp8 interaction with the 5' splice site.

Boesler C, Rigo N, Agafonov DE, Kastner B, Urlaub H, Will CL, Lührmann R.

RNA. 2015 Nov;21(11):1993-2005. doi: 10.1261/rna.053991.115. Epub 2015 Sep 18.


The RNA helicase Aquarius exhibits structural adaptations mediating its recruitment to spliceosomes.

De I, Bessonov S, Hofele R, dos Santos K, Will CL, Urlaub H, Lührmann R, Pena V.

Nat Struct Mol Biol. 2015 Feb;22(2):138-44. doi: 10.1038/nsmb.2951. Epub 2015 Jan 19.


Novel regulatory principles of the spliceosomal Brr2 RNA helicase and links to retinal disease in humans.

Mozaffari-Jovin S, Wandersleben T, Santos KF, Will CL, Lührmann R, Wahl MC.

RNA Biol. 2014;11(4):298-312. doi: 10.4161/rna.28353. Epub 2014 Mar 5. Review.


The Prp19 complex directly functions in mitotic spindle assembly.

Hofmann JC, Tegha-Dunghu J, Dräger S, Will CL, Lührmann R, Gruss OJ.

PLoS One. 2013 Sep 19;8(9):e74851. doi: 10.1371/journal.pone.0074851. eCollection 2013.


Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8.

Mozaffari-Jovin S, Wandersleben T, Santos KF, Will CL, Lührmann R, Wahl MC.

Science. 2013 Jul 5;341(6141):80-4. doi: 10.1126/science.1237515. Epub 2013 May 23.


The Prp8 RNase H-like domain inhibits Brr2-mediated U4/U6 snRNA unwinding by blocking Brr2 loading onto the U4 snRNA.

Mozaffari-Jovin S, Santos KF, Hsiao HH, Will CL, Urlaub H, Wahl MC, Lührmann R.

Genes Dev. 2012 Nov 1;26(21):2422-34. doi: 10.1101/gad.200949.112.


Post-transcriptional spliceosomes are retained in nuclear speckles until splicing completion.

Girard C, Will CL, Peng J, Makarov EM, Kastner B, Lemm I, Urlaub H, Hartmuth K, Lührmann R.

Nat Commun. 2012;3:994. doi: 10.1038/ncomms1998.


Dynamic protein-protein interaction wiring of the human spliceosome.

Hegele A, Kamburov A, Grossmann A, Sourlis C, Wowro S, Weimann M, Will CL, Pena V, Lührmann R, Stelzl U.

Mol Cell. 2012 Feb 24;45(4):567-80. doi: 10.1016/j.molcel.2011.12.034.


Semiquantitative proteomic analysis of the human spliceosome via a novel two-dimensional gel electrophoresis method.

Agafonov DE, Deckert J, Wolf E, Odenwälder P, Bessonov S, Will CL, Urlaub H, Lührmann R.

Mol Cell Biol. 2011 Jul;31(13):2667-82. doi: 10.1128/MCB.05266-11. Epub 2011 May 2.


Spliceosome structure and function.

Will CL, Lührmann R.

Cold Spring Harb Perspect Biol. 2011 Jul 1;3(7). pii: a003707. doi: 10.1101/cshperspect.a003707. Review.


HSPC117 is the essential subunit of a human tRNA splicing ligase complex.

Popow J, Englert M, Weitzer S, Schleiffer A, Mierzwa B, Mechtler K, Trowitzsch S, Will CL, Lührmann R, Söll D, Martinez J.

Science. 2011 Feb 11;331(6018):760-4. doi: 10.1126/science.1197847.


Characterization of purified human Bact spliceosomal complexes reveals compositional and morphological changes during spliceosome activation and first step catalysis.

Bessonov S, Anokhina M, Krasauskas A, Golas MM, Sander B, Will CL, Urlaub H, Stark H, Lührmann R.

RNA. 2010 Dec;16(12):2384-403. doi: 10.1261/rna.2456210. Epub 2010 Oct 27.


Exon definition complexes contain the tri-snRNP and can be directly converted into B-like precatalytic splicing complexes.

Schneider M, Will CL, Anokhina M, Tazi J, Urlaub H, Lührmann R.

Mol Cell. 2010 Apr 23;38(2):223-35. doi: 10.1016/j.molcel.2010.02.027.


An ancient mechanism for splicing control: U11 snRNP as an activator of alternative splicing.

Verbeeren J, Niemelä EH, Turunen JJ, Will CL, Ravantti JJ, Lührmann R, Frilander MJ.

Mol Cell. 2010 Mar 26;37(6):821-33. doi: 10.1016/j.molcel.2010.02.014.


Molecular architecture of the human Prp19/CDC5L complex.

Grote M, Wolf E, Will CL, Lemm I, Agafonov DE, Schomburg A, Fischle W, Urlaub H, Lührmann R.

Mol Cell Biol. 2010 May;30(9):2105-19. doi: 10.1128/MCB.01505-09. Epub 2010 Feb 22.


Human PRP4 kinase is required for stable tri-snRNP association during spliceosomal B complex formation.

Schneider M, Hsiao HH, Will CL, Giet R, Urlaub H, Lührmann R.

Nat Struct Mol Biol. 2010 Feb;17(2):216-21. doi: 10.1038/nsmb.1718. Epub 2010 Jan 31.


The spliceosome: design principles of a dynamic RNP machine.

Wahl MC, Will CL, Lührmann R.

Cell. 2009 Feb 20;136(4):701-18. doi: 10.1016/j.cell.2009.02.009. Review.


Conservation of the protein composition and electron microscopy structure of Drosophila melanogaster and human spliceosomal complexes.

Herold N, Will CL, Wolf E, Kastner B, Urlaub H, Lührmann R.

Mol Cell Biol. 2009 Jan;29(1):281-301. doi: 10.1128/MCB.01415-08. Epub 2008 Nov 3.


Minor spliceosome components are predominantly localized in the nucleus.

Pessa HK, Will CL, Meng X, Schneider C, Watkins NJ, Perälä N, Nymark M, Turunen JJ, Lührmann R, Frilander MJ.

Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8655-60. doi: 10.1073/pnas.0803646105. Epub 2008 Jun 16.


The U11-48K protein contacts the 5' splice site of U12-type introns and the U11-59K protein.

Turunen JJ, Will CL, Grote M, Lührmann R, Frilander MJ.

Mol Cell Biol. 2008 May;28(10):3548-60. doi: 10.1128/MCB.01928-07. Epub 2008 Mar 17.


Isolation of an active step I spliceosome and composition of its RNP core.

Bessonov S, Anokhina M, Will CL, Urlaub H, Lührmann R.

Nature. 2008 Apr 17;452(7189):846-50. doi: 10.1038/nature06842. Epub 2008 Mar 5.


Composition and three-dimensional EM structure of double affinity-purified, human prespliceosomal A complexes.

Behzadnia N, Golas MM, Hartmuth K, Sander B, Kastner B, Deckert J, Dube P, Will CL, Urlaub H, Stark H, Lührmann R.

EMBO J. 2007 Mar 21;26(6):1737-48. Epub 2007 Mar 1.


The 5' end of U2 snRNA is in close proximity to U1 and functional sites of the pre-mRNA in early spliceosomal complexes.

Dönmez G, Hartmuth K, Kastner B, Will CL, Lührmann R.

Mol Cell. 2007 Feb 9;25(3):399-411.


Protein composition of human mRNPs spliced in vitro and differential requirements for mRNP protein recruitment.

Merz C, Urlaub H, Will CL, Lührmann R.

RNA. 2007 Jan;13(1):116-28. Epub 2006 Nov 9.


Functional spliceosomal A complexes can be assembled in vitro in the absence of a penta-snRNP.

Behzadnia N, Hartmuth K, Will CL, Lührmann R.

RNA. 2006 Sep;12(9):1738-46. Epub 2006 Jul 31.


Protein composition and electron microscopy structure of affinity-purified human spliceosomal B complexes isolated under physiological conditions.

Deckert J, Hartmuth K, Boehringer D, Behzadnia N, Will CL, Kastner B, Stark H, Urlaub H, Lührmann R.

Mol Cell Biol. 2006 Jul;26(14):5528-43.


U2 snRNA-protein contacts in purified human 17S U2 snRNPs and in spliceosomal A and B complexes.

Dybkov O, Will CL, Deckert J, Behzadnia N, Hartmuth K, Lührmann R.

Mol Cell Biol. 2006 Apr;26(7):2803-16.


Splicing of a rare class of introns by the U12-dependent spliceosome.

Will CL, Lührmann R.

Biol Chem. 2005 Aug;386(8):713-24. Review.


The U11/U12 snRNP 65K protein acts as a molecular bridge, binding the U12 snRNA and U11-59K protein.

Benecke H, Lührmann R, Will CL.

EMBO J. 2005 Sep 7;24(17):3057-69. Epub 2005 Aug 11.


Identification of an evolutionarily divergent U11 small nuclear ribonucleoprotein particle in Drosophila.

Schneider C, Will CL, Brosius J, Frilander MJ, Lührmann R.

Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9584-9. Epub 2004 Jun 21.


A subset of human 35S U5 proteins, including Prp19, function prior to catalytic step 1 of splicing.

Makarova OV, Makarov EM, Urlaub H, Will CL, Gentzel M, Wilm M, Lührmann R.

EMBO J. 2004 Jun 16;23(12):2381-91. Epub 2004 Jun 3.


The human 18S U11/U12 snRNP contains a set of novel proteins not found in the U2-dependent spliceosome.

Will CL, Schneider C, Hossbach M, Urlaub H, Rauhut R, Elbashir S, Tuschl T, Lührmann R.

RNA. 2004 Jun;10(6):929-41.


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.

Pillai RS, Grimmler M, Meister G, Will CL, Lührmann R, Fischer U, Schümperli D.

Genes Dev. 2003 Sep 15;17(18):2321-33.


Molecular architecture of the multiprotein splicing factor SF3b.

Golas MM, Sander B, Will CL, Lührmann R, Stark H.

Science. 2003 May 9;300(5621):980-4.

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