Structures of Human Pumilio with Noncognate RNAs Reveal Molecular Mechanisms for Binding Promiscuity

Yogesh K. Gupta; Deepak T. Nair; Robin P. Wharton; Aneel K. Aggarwal

doi:10.1016/j.str.2008.01.006

Structures of Human Pumilio with Noncognate RNAs Reveal Molecular Mechanisms for Binding Promiscuity

Yogesh K. Gupta, Deepak T. Nair, Robin P. Wharton, Aneel K. Aggarwal

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycB_reverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a "spacer." The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.

Original language	English (US)
Pages (from-to)	549-557
Number of pages	9
Journal	Structure
Volume	16
Issue number	4
DOIs	https://doi.org/10.1016/j.str.2008.01.006
State	Published - Apr 8 2008
Externally published	Yes

Keywords

RNA

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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10.1016/j.str.2008.01.006

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title = "Structures of Human Pumilio with Noncognate RNAs Reveal Molecular Mechanisms for Binding Promiscuity",

abstract = "Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycBreverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a {"}spacer.{"} The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.",

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author = "Gupta, {Yogesh K.} and Nair, {Deepak T.} and Wharton, {Robin P.} and Aggarwal, {Aneel K.}",

note = "Funding Information: We thank the staff at Advanced Photon Source (beamlines 17-ID and 17-BM) and at Brookhaven National Laboratory (beamlines X4C and X6A) for facilitating X-ray data collection. We thank J. Seetharaman for help with data collection. This work was supported by grant GM062947 from the National Institutes of Health (A.K.A. and R.P.W.). R.P.W. is an Investigator of the Howard Hughes Medical Institute. ",

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AU - Gupta, Yogesh K.

AU - Nair, Deepak T.

AU - Wharton, Robin P.

AU - Aggarwal, Aneel K.

N1 - Funding Information: We thank the staff at Advanced Photon Source (beamlines 17-ID and 17-BM) and at Brookhaven National Laboratory (beamlines X4C and X6A) for facilitating X-ray data collection. We thank J. Seetharaman for help with data collection. This work was supported by grant GM062947 from the National Institutes of Health (A.K.A. and R.P.W.). R.P.W. is an Investigator of the Howard Hughes Medical Institute.

PY - 2008/4/8

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N2 - Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycBreverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a "spacer." The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.

AB - Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycBreverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a "spacer." The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.

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Structures of Human Pumilio with Noncognate RNAs Reveal Molecular Mechanisms for Binding Promiscuity

Abstract

Keywords

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