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Target RNA motif and target mRNAs of the Quaking STAR protein

André Galarneau1, Stéphane Richard

  • 1Terry Fox Molecular Oncology Group, Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Department of Oncology, McGill University, Montréal, Québec, Canada, H3T 1E2.

Nature Structural & Molecular Biology
|July 26, 2005
PubMed

Insights

Quaking (Qk) proteins bind specific RNA sequences, known as the QKI response element (QRE). This discovery identified thousands of new QK targets, revealing their crucial roles in development and potential links to cancer.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Quaking viable (Qk(v)) mice exhibit developmental defects and tremors.
  • The quaking (Qk) locus encodes STAR family RNA-binding proteins.

Purpose of the Study:

  • To characterize the RNA binding specificity of QKI proteins.
  • To identify novel RNA targets of QKI proteins.

Main Methods:

  • RNA selection assays were used to identify RNA species binding to QKI proteins.
  • The QKI response element (QRE) was defined as a bipartite consensus sequence.
  • Bioinformatic analysis using the QRE predicted new mRNA targets.
  • In vivo validation confirmed a subset of predicted targets.

Main Results:

  • The QKI response element (QRE) was identified as NACUAAY-N(1-20)-UAAY.
  • 1,430 new putative mRNA targets for QKI proteins were identified.
  • 23 novel mRNA targets were validated in vivo.
  • Validated targets are significantly enriched in genes involved in development, cell differentiation, growth, and maintenance.

Conclusions:

  • QKI proteins bind to a specific bipartite RNA sequence (QRE).
  • QKI proteins regulate a large number of mRNAs crucial for development and cell differentiation.
  • The identified targets suggest a potential role for QKI proteins in cancer.

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