Modular Recognition of RNA by a Human Pumilio-Homology Domain

Wang, Xiaoqiang; McLachlan, Juanita; Zamore, Phillip D.; Hall, Traci M. Tanaka

doi:10.1016/s0092-8674(02)00873-5

Cited by 458 publications

(724 citation statements)

References 31 publications

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“…The binding and translational repression requires the interaction of Puf6 protein with the consensus UUGU segments, known to be recognized by PUF family proteins (Wang et al 2002), in the 3ЈUTR of the ASH1 mRNA. Deletion of puf6 or mutation of the UUGU elements of the mRNA increased the intracellular Ash1p concentration and significantly affected asymmetric Ash1p segregation, evidently due to the disruption of the interaction between Puf6p and its target mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of the NLS suggested that Puf6p may be a nuclear protein. PUF proteins have been identified to function through interaction with the 3ЈUTRs of Drosophila hb mRNA, C. elegans fem-3 mRNA, and yeast HO mRNA (Wharton and Struhl 1991;Murata and Wharton 1995;Zhang et al 1997;Wharton et al 1998;Tadauchi et al 2001;Wang et al 2002). Although these 3ЈUTRs share little overall similarity to each other, they all contain the UUGU tetranucleotide, the conserved segment important for PUF protein function.…”

Section: Ash1 Mrna Contains Conserved Puf Recognition Sequences In Thmentioning

confidence: 99%

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A new yeast PUF family protein, Puf6p, represses ASH1 mRNA translation and is required for its localization

et al. 2004

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In yeast Saccharomyces cerevisiae, Ash1p, a protein determinant for mating-type switching, is segregated within the daughter cell nucleus to establish asymmetry of HO expression. The accumulation of Ash1p results from ASH1 mRNA that is sorted as a ribonucleoprotein particle (mRNP or locasome) to the distal tip of the bud where translation occurs. To study the mechanism regulating ASH1 mRNA translation, we isolated the ASH1 locasome and characterized the associated proteins by MALDI-TOF. One of these proteins was Puf6p, a new member of the PUF family of highly conserved RNA-binding proteins such as Pumilio in Drosophila, responsible for translational repression, usually to effect asymmetric expression. Puf6p-bound PUF consensus sequences in the 3 UTR of ASH1 mRNA and repressed the translation of ASH1 mRNA both in vivo and in vitro. In the puf6⌬ strain, asymmetric localization of both Ash1p and ASH1 mRNA were significantly reduced. We propose that Puf6p is a protein that functions in the translational control of ASH1 mRNA, and this translational inhibition is necessary before localization can proceed.

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Section: Discussionmentioning

confidence: 99%

Section: Ash1 Mrna Contains Conserved Puf Recognition Sequences In Thmentioning

confidence: 99%

A new yeast PUF family protein, Puf6p, represses ASH1 mRNA translation and is required for its localization

et al. 2004

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“…A recent and striking specific example (Fig. 3) comes from the Puf proteins or pumilio homology domains, which are a repeated a-helical structure in which each helical repeat supplies an amino acid side chain to stack on and sandwich successive bound RNA bases (Wang et al 2002). Thus by either of the above two means, an aromatic amino acid side chain may also be a group that strongly localizes an amino acid so that its adjacent profile may be determined.…”

Section: The Polar Profilementioning

confidence: 99%

“…This description should not be thought of as exhaustive; for example, SAM I and SAM III use a syn Fig. 3 Stereo pair of nucleobase-amino acid stacking within the human pumiliohomology domain bound to RNA (Wang et al 2002). The magenta projections from the arc of a-helical repeats on the right are stacked amino acid side chains from position 13 of each pumilio-homology domain repeat.…”

Section: The Polar Profilementioning

confidence: 99%

RNA–Amino Acid Binding: A Stereochemical Era for the Genetic Code

2009

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By combining crystallographic and NMR structural data for RNA-bound amino acids within riboswitches, aptamers, and RNPs, chemical principles governing specific RNA interaction with amino acids can be deduced. Such principles, which we summarize in a ''polar profile'', are useful in explaining newly selected specific RNA binding sites for free amino acids bearing varied side chains charged, neutral polar, aliphatic, and aromatic. Such amino acid sites can be queried for parallels to the genetic code. Using recent sequences for 337 independent binding sites directed to 8 amino acids and containing 18,551 nucleotides in all, we show a highly robust connection between amino acids and cognate coding triplets within their RNA binding sites. The apparent probability (P) that cognate triplets around these sites are unrelated to binding sites is %5.3 9 10 -45 for codons overall, and P % 2.1 9 10 -46 for cognate anticodons. Therefore, some triplets are unequivocally localized near their present amino acids. Accordingly, there was likely a stereochemical era during evolution of the genetic code, relying on chemical interactions between amino acids and the tertiary structures of RNA binding sites. Use of cognate coding triplets in RNA binding sites is nevertheless sparse, with only 21% of possible triplets appearing. Reasoning from such broad recurrent trends in our results, a majority (approximately 75%) of modern amino acids entered the code in this stereochemical era; nevertheless, a minority (approximately 21%) of modern codons and anticodons were assigned via RNA binding sites.A Direct RNA Template scheme embodying a credible early history for coded peptide synthesis is readily constructed based on these observations.

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“…Stacking interactions involving tyrosine or phenylalanine are more common. The Tis11d ZnFs, which recognize AU-rich elements (24), and the pumilio repeat proteins, which bind elements in the 3Ј untranslated regions of target mRNAs (25), both display such stacks.…”

Section: The Binding Preferences Of Zranb2 Corroborate Functional Splmentioning

confidence: 99%

The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5′ splice site-like sequences

Loughlin

Mansfield

Vaz

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The alternative splicing of mRNA is a critical process in higher eukaryotes that generates substantial proteomic diversity. Many of the proteins that are essential to this process contain arginine/serine-rich (RS) domains. ZRANB2 is a widely-expressed and highly-conserved RS-domain protein that can regulate alternative splicing but lacks canonical RNA-binding domains. Instead, it contains 2 RanBP2-type zinc finger (ZnF) domains. We demonstrate that these ZnFs recognize ssRNA with high affinity and specificity. Each ZnF binds to a single AGGUAA motif and the 2 domains combine to recognize AGGUAA (Nx)AGGUAA double sites, suggesting that ZRANB2 regulates alternative splicing via a direct interaction with pre-mRNA at sites that resemble the consensus 5 splice site. We show using X-ray crystallography that recognition of an AGGUAA motif by a single ZnF is dominated by side-chain hydrogen bonds to the bases and formation of a guanine-tryptophan-guanine ''ladder.'' A number of other human proteins that function in RNA processing also contain RanBP2 ZnFs in which the RNA-binding residues of ZRANB2 are conserved. The ZnFs of ZRANB2 therefore define another class of RNA-binding domain, advancing our understanding of RNA recognition and emphasizing the versatility of ZnF domains in molecular recognition.protein structure ͉ RanBP2 zinc fingers ͉ RNA-binding proteins ͉ splicing A lmost all human genes are thought to be alternatively spliced, and it has been estimated that at least 15% of human diseases are associated with changes in RNA processing (1). The selection of splice sites is influenced heavily by the binding of accessory splicing factors to regulatory sequences in the pre-mRNA. SR proteins are splicing factors that contain a C-terminal Arg/Ser-rich (RS) domain and either 1 or 2 N-terminal RNA recognition motifs (RRMs) (2). They play crucial roles in constitutive and alternative splicing, promoting recognition of splice sites by binding to exonic splicing enhancers (ESEs). RRM domains bind ssRNA with high affinity in a sequence-specific manner, whereas RS domains appear to facilitate both protein-protein and protein-RNA interactions (3, 4). Other RS domain-containing proteins that lack a canonical RRM, termed ''SR-like'' proteins (see, for example, ref. 5) are also known to play roles in splicing.ZRANB2 (Zis, ZNF265) is an SR-like nuclear protein that is expressed in most tissues and is conserved between nematodes and mammals. It interacts with the spliceosomal proteins U1-70K and U2AF 35 and can alter the distribution of splice variants of GluR-B, SMN2, and Tra2␤ in minigene reporter assays (6, 7). As such, ZRANB2 appears to regulate splice site choice. However, in place of the canonical RNA-binding RRM domains, ZRANB2 displays 2 N-terminal RanBP2-type zinc fingers (ZnFs).RanBP2-type ZnF domains are defined by the consensus sequence W-X-C-X 2-4 -C-X 3 -N-X 6 -C-X 2 -C. They occur multiple times in at least 21 human proteins, and the fold comprises 2 distorted ␤-hairpins sandwiching a central tryptophan residue and ...

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Modular Recognition of RNA by a Human Pumilio-Homology Domain

Cited by 458 publications

References 31 publications

A new yeast PUF family protein, Puf6p, represses ASH1 mRNA translation and is required for its localization

A new yeast PUF family protein, Puf6p, represses ASH1 mRNA translation and is required for its localization

RNA–Amino Acid Binding: A Stereochemical Era for the Genetic Code

The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5′ splice site-like sequences

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