The structural basis for RNA selectivity by the IMP family of RNA-binding proteins

Jeetayu Biswas, Vivek L. Patel, Varun Bhaskar, Jeffrey A. Chao, Robert H. Singer, Carolina Eliscovich

Research output: Contribution to journalArticle

Abstract

The IGF2 mRNA-binding proteins (ZBP1/IMP1, IMP2, IMP3) are highly conserved post-transcriptional regulators of RNA stability, localization and translation. They play important roles in cell migration, neural development, metabolism and cancer cell survival. The knockout phenotypes of individual IMP proteins suggest that each family member regulates a unique pool of RNAs, yet evidence and an underlying mechanism for this is lacking. Here, we combine systematic evolution of ligands by exponential enrichment (SELEX) and NMR spectroscopy to demonstrate that the major RNA-binding domains of the two most distantly related IMPs (ZBP1 and IMP2) bind to different consensus sequences and regulate targets consistent with their knockout phenotypes and roles in disease. We find that the targeting specificity of each IMP is determined by few amino acids in their variable loops. As variable loops often differ amongst KH domain paralogs, we hypothesize that this is a general mechanism for evolving specificity and regulation of the transcriptome.

Original languageEnglish (US)
Article number4440
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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IMP
Inosine Monophosphate
RNA-Binding Proteins
phenotype
selectivity
RNA
proteins
SELEX Aptamer Technique
Phenotype
regulators
RNA Stability
Consensus Sequence
metabolism
Transcriptome
Metabolism
Nuclear magnetic resonance spectroscopy
Cell Movement
amino acids
Cell Survival
Carrier Proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

The structural basis for RNA selectivity by the IMP family of RNA-binding proteins. / Biswas, Jeetayu; Patel, Vivek L.; Bhaskar, Varun; Chao, Jeffrey A.; Singer, Robert H.; Eliscovich, Carolina.

In: Nature communications, Vol. 10, No. 1, 4440, 01.12.2019.

Research output: Contribution to journalArticle

Biswas, Jeetayu ; Patel, Vivek L. ; Bhaskar, Varun ; Chao, Jeffrey A. ; Singer, Robert H. ; Eliscovich, Carolina. / The structural basis for RNA selectivity by the IMP family of RNA-binding proteins. In: Nature communications. 2019 ; Vol. 10, No. 1.
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