Role of the amino terminal RHAU-specific motif in the recognition and resolution of guanine quadruplex-RNA by the DEAH-box RNA helicase RHAU.
Under physiological conditions, guanine-rich sequences of DNA and RNA can adopt stable and atypical four-stranded helical structures called G-quadruplexes (G4). Such G4 structures have been shown to occur in vivo and to play a role in various processes such as transcription, translation and telomere maintenance. Owing to their high-thermodynamic stability, resolution of G4 structures in vivo requires specialized enzymes. RHAU is a human RNA helicase of the DEAH-box family that exhibits a unique ATP-dependent G4-resolvase activity with a high affinity and specificity for its substrate in vitro. How RHAU recognizes G4-RNAs has not yet been established. Here, we show that the amino-terminal region of RHAU is essential for RHAU to bind G4 structures and further identify within this region the evolutionary conserved RSM (RHAU-specific motif) domain as a major affinity and specificity determinant. G4-resolvase activity and strict RSM dependency are also observed with CG9323, the Drosophila orthologue of RHAU, in the amino terminal region of which the RSM is the only conserved motif. Thus, these results reveal a novel motif in RHAU protein that plays an important role in recognizing and resolving G4-RNA structures, properties unique to RHAU among many known RNA helicases.
Lattmann
Simon
S
Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Giri
Banabihari
B
Vaughn
James P
JP
Akman
Steven A
SA
Nagamine
Yoshikuni
Y
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000201:enzymology; D054856:G-Quadruplexes; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion
D012313:RNA; D000251:Adenosine Triphosphatases; C466988:DHX36 protein, human; D053487:DEAD-box RNA Helicases
J Biol Chem. 2001 Jun 15;276(24):21184-91
11283007
J Mol Biol. 2002 Dec 6;324(4):625-36
12460566
Cell. 2002 Jun 28;109(7):797-800
12110176
RNA. 1998 Oct;4(10):1216-29
9769096
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11593-8
12195017
Structure. 1998 Jan 15;6(1):89-100
9493270
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D119-24
16381828
J Biol Chem. 1998 Oct 16;273(42):27587-92
9765292
Gene. 2003 Jul 17;312:1-16
12909336
J Biol Chem. 2008 Dec 26;283(52):36132-9
18978354
J Mol Biol. 2008 Feb 1;375(5):1344-64
18096186
Trends Biochem Sci. 1999 May;24(5):192-8
10322435
RNA. 2008 Jul;14(7):1290-6
18515550
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W197-201
18463136
J Biol Chem. 2008 Dec 12;283(50):34626-34
18842585
Nat Rev Cancer. 2009 Sep;9(9):644-54
19657341
Curr Opin Mol Ther. 2009 Apr;11(2):146-55
19330720
Nucleic Acids Res. 2006;34(15):4181-8
16935886
Nucleic Acids Res. 2008 Oct;36(17):5482-515
18718931
Mol Cell. 2004 Jan 16;13(1):101-11
14731398
Mol Cell Biol. 2008 Jun;28(12):4116-28
18426915
J Biol Chem. 2005 Oct 21;280(42):35499-505
16118224
Nat Chem Biol. 2007 Apr;3(4):218-21
17322877
Cell. 2006 Apr 21;125(2):287-300
16630817
Nat Rev Genet. 2007 Oct;8(10):735-48
17768402
Nat Struct Mol Biol. 2006 Dec;13(12):1055-9
17146462
Gene. 1989 Apr 15;77(1):51-9
2744487
Front Biosci. 2008 Jan 01;13:1-20
17981525
Biochemistry. 2009 Jun 16;48(23):5313-9
19397366
Nucleic Acids Res. 1999 Oct 1;27(19):3811-20
10481020
Mol Cell. 2001 Aug;8(2):251-62
11545728
Nat Rev Mol Cell Biol. 2004 Mar;5(3):232-41
14991003
RNA. 2001 May;7(5):702-9
11350034
J Biol Chem. 2008 Dec 12;283(50):35186-98
18854321
Nucleic Acids Res. 2006;34(15):4168-80
16936318
Mol Cell. 2007 Aug 3;27(3):339-52
17679086
J Bacteriol. 2002 Apr;184(7):1819-26
11889086
Nat Struct Mol Biol. 2009 Mar;16(3):247-54
19219046
Genes Dev. 1996 Apr 15;10(8):997-1007
8608946
Nucleic Acids Res. 2004 Aug 10;32(14):e115
15304544
Gene. 1989 Apr 15;77(1):61-8
2744488
Nucleic Acids Res. 2004 Aug 09;32(14):4145-54
15302914
Cell Mol Life Sci. 2009 Apr;66(7):1209-22
19099189
EMBO J. 1993 Sep;12(9):3619-26
8253085
Chem Biol. 2007 Jul;14(7):757-63
17656312
Nucleic Acids Res. 2008 Feb;36(3):950-62
18086708
EMBO J. 2001 Oct 1;20(19):5503-12
11574482
J Biol Chem. 2005 Nov 18;280(46):38117-20
16150737
Mol Cell. 2009 Sep 11;35(5):598-609
19748356
Nucleic Acids Res. 1994 Jul 11;22(13):2552-6
8041617
J Biol Chem. 1996 Dec 27;271(52):33261-7
8969184
Front Biosci. 2007 May 01;12:4336-51
17485378
Trends Biochem Sci. 2008 Mar;33(3):141-50
18291657
Biol Chem. 2009 Dec;390(12):1237-50
19747077
Biochemistry. 2006 May 23;45(20):6510-21
16700561
J Cell Biol. 2006 Mar 13;172(6):803-8
16520386
J Biol Chem. 2009 Apr 17;284(16):10296-300
19244245
Nucleic Acids Res. 2002 Sep 15;30(18):3954-61
12235379
Gene. 2006 Feb 15;367:17-37
16337753
Biochimie. 2008 Aug;90(8):1149-71
18355457
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13857-62
14610285
Brief Bioinform. 2008 Jul;9(4):286-98
18372315
Biochemistry. 2007 Mar 20;46(11):3013-22
17311413
FEBS Lett. 2002 Feb 20;513(1):141-4
11911894
J Biol Chem. 1999 Apr 30;274(18):12797-802
10212265
J Biol Chem. 2004 Mar 5;279(10):8617-26
14688266