BRR2

Summary

Gene Symbol: BRR2
Description: ATP-dependent RNA helicase BRR2
Alias: PRP44, RSS1, SLT22, SNU246, ATP-dependent RNA helicase BRR2
Species: Saccharomyces cerevisiae S288c
Products:     BRR2

Top Publications

  1. Hahn D, Kudla G, Tollervey D, Beggs J. Brr2p-mediated conformational rearrangements in the spliceosome during activation and substrate repositioning. Genes Dev. 2012;26:2408-21 pubmed publisher
    ..Consistent with this, mutant brr2-G858R reduced second-step splicing efficiency and enhanced cross-linking to 3' ends of introns...
  2. Zhang L, Xu T, Maeder C, Bud L, Shanks J, Nix J, et al. Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2. Nat Struct Mol Biol. 2009;16:731-9 pubmed publisher
    b>Brr2 is a DExD/H-box helicase responsible for U4/U6 unwinding during spliceosomal activation. Brr2 contains two helicase-like domains, each of which is followed by a Sec63 domain with unknown function...
  3. Maeder C, Kutach A, Guthrie C. ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8. Nat Struct Mol Biol. 2009;16:42-8 pubmed publisher
    ..A fundamental unanswered question is how their activities are regulated. Brr2 function is necessary for unwinding the U4/U6 duplex, a step essential for catalytic activation of the spliceosome...
  4. Boon K, Grainger R, Ehsani P, Barrass J, Auchynnikava T, Inglehearn C, et al. prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast. Nat Struct Mol Biol. 2007;14:1077-83 pubmed
    ..We therefore propose a novel assembly pathway for U5 snRNP complexes that is disrupted by mutations that cause human RP. ..
  5. Xu D, Nouraini S, Field D, Tang S, Friesen J. An RNA-dependent ATPase associated with U2/U6 snRNAs in pre-mRNA splicing. Nature. 1996;381:709-13 pubmed
    ..X. et al., manuscript in preparation). The RNA-dependent ATPase activity associated with one such factor, the Slt22 protein, is stimulated preferentially by annealed U2/U6 snRNAs...
  6. Brenner T, Guthrie C. Genetic analysis reveals a role for the C terminus of the Saccharomyces cerevisiae GTPase Snu114 during spliceosome activation. Genetics. 2005;170:1063-80 pubmed
    ..was synthetically lethal with factors required for activation of the spliceosome, including the DExD/H-box ATPases BRR2 and PRP28...
  7. Brenner T, Guthrie C. Assembly of Snu114 into U5 snRNP requires Prp8 and a functional GTPase domain. RNA. 2006;12:862-71 pubmed
    ..between SNU114 and genes encoding three other U5 snRNP components, Prp8 and two RNA-dependent ATPases, Prp28 and Brr2, required for destabilization of U1 and U4 snRNPs prior to catalysis...
  8. Mozaffari Jovin S, Santos K, Hsiao H, Will C, Urlaub H, Wahl M, et al. The Prp8 RNase H-like domain inhibits Brr2-mediated U4/U6 snRNA unwinding by blocking Brr2 loading onto the U4 snRNA. Genes Dev. 2012;26:2422-34 pubmed publisher
    The spliceosomal RNA helicase Brr2 catalyzes unwinding of the U4/U6 snRNA duplex, an essential step for spliceosome catalytic activation. Brr2 is regulated in part by the spliceosomal Prp8 protein by an unknown mechanism...
  9. Small E, Leggett S, Winans A, Staley J. The EF-G-like GTPase Snu114p regulates spliceosome dynamics mediated by Brr2p, a DExD/H box ATPase. Mol Cell. 2006;23:389-99 pubmed
    ..We propose that Snu114p serves as a signal-dependent switch that transduces signals to Brr2p to control spliceosome dynamics. ..

More Information

Publications36

  1. Lauber J, Fabrizio P, Teigelkamp S, Lane W, Hartmann E, Luhrmann R. The HeLa 200 kDa U5 snRNP-specific protein and its homologue in Saccharomyces cerevisiae are members of the DEXH-box protein family of putative RNA helicases. EMBO J. 1996;15:4001-15 pubmed
    ..Disruption of the SNU246 gene in yeast is lethal and leads to a splicing defect in vivo, indicating that the protein is essential for ..
  2. Weber G, Cristão V, de L Alves F, Santos K, Holton N, Rappsilber J, et al. Mechanism for Aar2p function as a U5 snRNP assembly factor. Genes Dev. 2011;25:1601-12 pubmed publisher
    ..The purpose of this regulation may be to safeguard against nonspecific RNA binding to Prp8p and/or premature activation of Brr2p activity. ..
  3. Häcker I, Sander B, Golas M, Wolf E, Karagöz E, Kastner B, et al. Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy. Nat Struct Mol Biol. 2008;15:1206-12 pubmed publisher
    ..activation that requires several components of the U5 portion of the tri-snRNP, including the RNA helicase Brr2, Prp8 and the GTPase Snu114. Here we report the EM projection structure of the Saccharomyces cerevisiae tri-snRNP...
  4. Boon K, Norman C, Grainger R, Newman A, Beggs J. Prp8p dissection reveals domain structure and protein interaction sites. RNA. 2006;12:198-205 pubmed
    ..Thus, the U5 snRNP protein Snu114p associates with Prp8p in the region 437-770, whereas fragmenting Prp8p at residue 2173 destabilizes its association with Aar2p. ..
  5. Raghunathan P, Guthrie C. RNA unwinding in U4/U6 snRNPs requires ATP hydrolysis and the DEIH-box splicing factor Brr2. Curr Biol. 1998;8:847-55 pubmed
    ..We have immunopurified Brr2, a DEIH-box ATPase, in a native complex containing U1, U2, U5 and duplex U4/U6 small nuclear ribonucleoprotein ..
  6. Kuhn A, Reichl E, Brow D. Distinct domains of splicing factor Prp8 mediate different aspects of spliceosome activation. Proc Natl Acad Sci U S A. 2002;99:9145-9 pubmed
    ..spliceosome is thought to require unwinding of the U1 RNA/5' splice site and U4/U6 RNA helices by the Prp28 and Prp44/Brr2 DExD/H-box helicases, respectively...
  7. Bouveret E, Rigaut G, Shevchenko A, Wilm M, Seraphin B. A Sm-like protein complex that participates in mRNA degradation. EMBO J. 2000;19:1661-71 pubmed
    ..These results indicate the involvement of a new conserved Sm-like protein complex and a new factor, Pat1p, in mRNA degradation and suggest a physical connection between decapping and exonuclease trimming. ..
  8. Huang Y, Chung C, Kao D, Kao T, Cheng S. Sad1 counteracts Brr2-mediated dissociation of U4/U6.U5 in tri-snRNP homeostasis. Mol Cell Biol. 2014;34:210-20 pubmed publisher
    ..b>Brr2 is responsible for mediating ATP-dependent dissociation of the tri-snRNP...
  9. Coltri P, Oliveira C. Cwc24p is a general Saccharomyces cerevisiae splicing factor required for the stable U2 snRNP binding to primary transcripts. PLoS ONE. 2012;7:e45678 pubmed publisher
    ..We propose a model in which Cwc24p is required for stabilizing the U2 association with primary transcripts, and therefore, especially important for splicing of RNAs containing non-consensus branchpoint sequences. ..
  10. Tsai R, Tseng C, Lee P, Chen H, Fu R, Chang K, et al. Dynamic interactions of Ntr1-Ntr2 with Prp43 and with U5 govern the recruitment of Prp43 to mediate spliceosome disassembly. Mol Cell Biol. 2007;27:8027-37 pubmed
    ..The NTR complex also dynamically interacts with U5 snRNP. Ntr2 interacts with U5 component Brr2 and is essential for both interactions of NTR with U5 and with the spliceosome...
  11. Gahura O, Abrhámová K, Skruzny M, Valentová A, Munzarová V, Folk P, et al. Prp45 affects Prp22 partition in spliceosomal complexes and splicing efficiency of non-consensus substrates. J Cell Biochem. 2009;106:139-51 pubmed publisher
    ..Our data suggest that Prp45 contributes, in part through its interaction with the 2nd step-proofreading helicase Prp22, to splicing efficiency of substrates non-conforming to the consensus. ..
  12. Nancollis V, Ruckshanthi J, Frazer L, O Keefe R. The U5 snRNA internal loop 1 is a platform for Brr2, Snu114 and Prp8 protein binding during U5 snRNP assembly. J Cell Biochem. 2013;114:2770-84 pubmed publisher
    ..The proteins Prp8, Snu114 and Brr2 all assemble with the U5 small nuclear RNA (snRNA) to produce the U5 snRNP...
  13. Nguyen T, Li J, Galej W, Oshikane H, Newman A, Nagai K. Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site. Structure. 2013;21:910-19 pubmed
    The U5 small nuclear ribonucleoprotein particle (snRNP) helicase Brr2 disrupts the U4/U6 small nuclear RNA (snRNA) duplex and allows U6 snRNA to engage in an intricate RNA network at the active center of the spliceosome...
  14. Absmeier E, Becke C, Wollenhaupt J, Santos K, Wahl M. Interplay of cis- and trans-regulatory mechanisms in the spliceosomal RNA helicase Brr2. Cell Cycle. 2017;16:100-112 pubmed publisher
    RNA helicase Brr2 is implicated in multiple phases of pre-mRNA splicing and thus requires tight regulation...
  15. Taoka M, Yamauchi Y, Nobe Y, Masaki S, Nakayama H, Ishikawa H, et al. An analytical platform for mass spectrometry-based identification and chemical analysis of RNA in ribonucleoprotein complexes. Nucleic Acids Res. 2009;37:e140 pubmed publisher
  16. Liu H, Cheng S. The interaction of Prp2 with a defined region of the intron is required for the first splicing reaction. Mol Cell Biol. 2012;32:5056-66 pubmed publisher
    ..We also show that Prp2 directly interacts with the carboxyl-terminal fragment of Brr2 by pulldown assays...
  17. Chen H, Tseng C, Tsai R, Chung C, Cheng S. Link of NTR-mediated spliceosome disassembly with DEAH-box ATPases Prp2, Prp16, and Prp22. Mol Cell Biol. 2013;33:514-25 pubmed publisher
    ..and Ntr2 to form the NTR complex and is recruited to the spliceosome via the interaction of Ntr2 and U5 component Brr2. Ntr2 alone can bind to U5 and to the spliceosome...
  18. Absmeier E, Wollenhaupt J, Mozaffari Jovin S, Becke C, Lee C, Preussner M, et al. The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation. Genes Dev. 2015;29:2576-87 pubmed publisher
    The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated...
  19. Masciadri B, Areces L, Carpinelli P, Foiani M, Draetta G, Fiore F. Characterization of the BUD31 gene of Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2004;320:1342-50 pubmed
    ..We propose that the observed phenotypes for bud31-null strain could be the result of defective splicing and indicate a first functional role for Bud3lp and its homologs. ..
  20. Weber G, Cristão V, Santos K, Jovin S, Heroven A, Holton N, et al. Structural basis for dual roles of Aar2p in U5 snRNP assembly. Genes Dev. 2013;27:525-40 pubmed publisher
    ..is assembled via a cytoplasmic precursor that contains the U5-specific Prp8 protein but lacks the U5-specific Brr2 helicase. Instead, pre-U5 snRNP includes the Aar2 protein not found in mature U5 snRNP or spliceosomes...
  21. Hoskins A, Friedman L, Gallagher S, Crawford D, Anderson E, Wombacher R, et al. Ordered and dynamic assembly of single spliceosomes. Science. 2011;331:1289-95 pubmed publisher
    ..This experimental strategy should prove widely useful for mechanistic analysis of other macromolecular machines in environments approaching the complexity of living cells. ..
  22. Ledoux S, Guthrie C. Retinitis Pigmentosa Mutations in Bad Response to Refrigeration 2 (Brr2) Impair ATPase and Helicase Activity. J Biol Chem. 2016;291:11954-65 pubmed publisher
    b>Brr2 is an RNA-dependent ATPase required to unwind the U4/U6 snRNA duplex during spliceosome assembly...
  23. Hoskins A, Rodgers M, Friedman L, Gelles J, Moore M. Single molecule analysis reveals reversible and irreversible steps during spliceosome activation. elife. 2016;5: pubmed publisher
    ..The data reveal the activation mechanism and show that overall splicing efficiency may be maintained through repeated rounds of disassembly and tri-snRNP reassociation. ..
  24. Dreumont N, Seraphin B. Rapid screening of yeast mutants with reporters identifies new splicing phenotypes. FEBS J. 2013;280:2712-26 pubmed publisher
    ..Thus, using appropriate reporters, yeast can be used to quickly delineate the effect of various factors on splicing and identify those with the propensity to regulate alternative splicing events. ..
  25. Görnemann J, Kotovic K, Hujer K, Neugebauer K. Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the cap binding complex. Mol Cell. 2005;19:53-63 pubmed
    ..Thus, the demonstration of an essential link between CBC and spliceosome assembly in vivo indicates that 5' end capping couples pre-mRNA splicing to transcription. ..
  26. Price A, Görnemann J, Guthrie C, Brow D. An unanticipated early function of DEAD-box ATPase Prp28 during commitment to splicing is modulated by U5 snRNP protein Prp8. RNA. 2014;20:46-60 pubmed publisher
    ..We conclude that the U5 snRNP has a role in the earliest events of assembly, prior to its stable incorporation into the spliceosome. ..
  27. Chanarat S, Seizl M, Strasser K. The Prp19 complex is a novel transcription elongation factor required for TREX occupancy at transcribed genes. Genes Dev. 2011;25:1147-58 pubmed publisher