Molecular architecture and dynamics of ASH1 mRNA recognition by its mRNA-transport complex

Nat Struct Mol Biol. 2017 Feb;24(2):152-161. doi: 10.1038/nsmb.3351. Epub 2017 Jan 16.

Abstract

mRNA localization is an essential mechanism of gene regulation and is required for processes such as stem-cell division, embryogenesis and neuronal plasticity. It is not known which features in the cis-acting mRNA localization elements (LEs) are specifically recognized by motor-containing transport complexes. To the best of our knowledge, no high-resolution structure is available for any LE in complex with its cognate protein complex. Using X-ray crystallography and complementary techniques, we carried out a detailed assessment of an LE of the ASH1 mRNA from yeast, its complex with its shuttling RNA-binding protein She2p, and its highly specific, cytoplasmic complex with She3p. Although the RNA alone formed a flexible stem loop, She2p binding induced marked conformational changes. However, only joining by the unstructured She3p resulted in specific RNA recognition. The notable RNA rearrangements and joint action of a globular and an unfolded RNA-binding protein offer unprecedented insights into the step-wise maturation of an mRNA-transport complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Inverted Repeat Sequences
  • Models, Molecular
  • Protein Binding
  • RNA Transport
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • ASH1 protein, S cerevisiae
  • RNA, Messenger
  • RNA-Binding Proteins
  • Repressor Proteins
  • SHE2 protein, S cerevisiae
  • SHE3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins