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Author Notes:

To whom correspondence should be addressed: Gary J. Bassell. Tel: +1 404 727 3772; Fax: +1 404 727 6256; Email: gbassel@emory.edu. Correspondence may also be addressed to Stephen T. Warren. Tel: +1 404 727-5979; Fax: +1 404 727 3949; Email: swarren@emory.edu.

Bart R. Anderson and Pankaj Chopra contributed equally to the paper as first authors.

Conflict of interest statement. None declared.

Subjects:

Research Funding:

National Institutes of Health [T32MH087977 to B.R.A., J.A.S., 1F32NS083205 to B.R.A, NS091859 to S.T.W., 1R01MH109026 to G.J.B].

Funding for open access charge: Departmental funds.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • MENTAL-RETARDATION PROTEIN
  • FRAGILE-X-SYNDROME
  • SEQUENCE-ANALYSIS TOOLS
  • G-QUADRUPLEX STRUCTURES
  • MESSENGER-RNA
  • INTERACTS
  • MOTIF
  • TRANSLATION
  • RECOGNITION
  • STABILITY

Identification of consensus binding sites clarifies FMRP binding determinants

Tools:

Journal Title:

Nucleic Acids Research

Volume:

Volume 44, Number 14

Publisher:

, Pages 6649-6659

Type of Work:

Article | Final Publisher PDF

Abstract:

Fragile X mental retardation protein (FMRP) is a multifunctional RNA-binding protein with crucial roles in neuronal development and function. Efforts aimed at elucidating how FMRP target mRNAs are selected have produced divergent sets of target mRNA and putative FMRP-bound motifs, and a clear understanding of FMRP's binding determinants has been lacking. To clarify FMRP's binding to its target mRNAs, we produced a shared dataset of FMRP consensus binding sequences (FCBS), which were reproducibly identified in two published FMRP CLIP sequencing datasets. This comparative dataset revealed that of the various sequence and structural motifs that have been proposed to specify FMRP binding, the short sequence motifs TGGA and GAC were corroborated, and a novel TAY motif was identified. In addition, the distribution of the FCBS set demonstrates that FMRP preferentially binds to the coding region of its targets but also revealed binding along 3′ UTRs in a subset of target mRNAs. Beyond probing these putative motifs, the FCBS dataset of reproducibly identified FMRP binding sites is a valuable tool for investigating FMRP targets and function.

Copyright information:

© 2016 The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. For commercial re-use, please contact journal.permissions@oup.com.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/).

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