Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d.
The tandem zinc finger (TZF) domain of the protein TIS11d binds to the class II AU-rich element (ARE) in the 3' untranslated region (3' UTR) of target mRNAs and promotes their deadenylation and degradation. The NMR structure of the TIS11d TZF domain bound to the RNA sequence 5'-UUAUUUAUU-3' comprises a pair of novel CCCH fingers of type CX(8)CX(5)CX(3)H separated by an 18-residue linker. The two TIS11d zinc fingers bind in a symmetrical fashion to adjacent 5'-UAUU-3' subsites on the single-stranded RNA via a combination of electrostatic and hydrogen-bonding interactions, with intercalative stacking between conserved aromatic side chains and the RNA bases. Sequence specificity in RNA recognition is achieved by a network of intermolecular hydrogen bonds, mostly between TIS11d main-chain functional groups and the Watson-Crick edges of the bases. The TIS11d structure provides insights into the RNA-binding functions of this large family of CCCH zinc finger proteins.
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Brian P
BP
Hudson
Maria A
MA
Martinez-Yamout
H Jane
HJ
Dyson
Peter E
PE
Wright
D020413:3' Untranslated Regions / Q000737:chemistry / Q000378:metabolism; D000225:Adenine; D001482:Base Composition; D001665:Binding Sites; D004268:DNA-Binding Proteins; D006801:Humans; D006860:Hydrogen Bonding; D017874:Immediate-Early Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D051816:Tristetraprolin; D014498:Uracil; D016335:Zinc Fingers
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D014498:Uracil; D000225:Adenine