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Alternate modes of cognate RNA recognition by human PUMILIO proteins

Gang Lu1, Traci M Tanaka Hall

  • 1Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.

Structure (London, England : 1993)
|March 15, 2011
PubMed

Insights

Human PUMILIO proteins (PUM1 and PUM2) bind target mRNAs through distinct structural modes. These varied binding patterns influence how PUM1 and PUM2 interact with other proteins, impacting gene regulation.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Genetics

Background:

  • Human PUMILIO1 (PUM1) and PUMILIO2 (PUM2) are key regulators of gene expression at the post-transcriptional level.
  • These proteins belong to the PUMILIO/FBF (PUF) family, known for their role in mRNA regulation.
  • Previous research has identified numerous mRNA targets for human PUM1 and PUM2.

Purpose of the Study:

  • To investigate the structural mechanisms underlying the recognition of natural mRNA targets by human PUF proteins.
  • To elucidate how PUM1 and PUM2 interact with specific RNA sequences, including those from MAP kinase mRNAs.

Main Methods:

  • Determined crystal structures of the RNA-binding domains of human PUM1 and PUM2.
  • Complexed these domains with four cognate RNA sequences, including segments from p38α and erk2 MAP kinase mRNAs.

Main Results:

  • Observed three distinct modes of RNA binding, particularly around the fifth RNA base.
  • Two of these binding modes differ from the previously established 1 repeat:1 RNA base binding mode.
  • In vitro RNA-binding affinities of PUM1 and PUM2 were largely unaffected by these different binding modes.

Conclusions:

  • The diverse RNA binding modes create variable recognition surfaces for PUF:RNA complexes.
  • These structural variations suggest a mechanism for recruiting downstream effector proteins in vivo.
  • Understanding these structural dynamics is crucial for deciphering PUM1 and PUM2's role in gene regulation.

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