Related Experiment Video

Updated: Jan 13, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

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ICAM1 mRNA entraps ILF2/ILF3 to inhibit transcription of EIF4E and global protein synthesis

Siyuan Jiang1, Jinghan Sun2, Ya Gao3

  • 1Zhongda Hospital, Medical School, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China.

Molecular Cell
|January 9, 2026
PubMed

Insights

Intercellular adhesion molecule 1 (ICAM1) mRNA regulates transcription independently of its protein. This discovery challenges gene silencing explanations and highlights novel mRNA functions.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The traditional view of messenger RNA (mRNA) solely as a template for protein translation is evolving.
  • The non-canonical functions of mRNA, independent of protein-coding, are not well understood.
  • Investigating these independent roles is crucial for a comprehensive understanding of gene regulation.

Purpose of the Study:

  • To explore the non-canonical functions of intercellular adhesion molecule 1 (ICAM1) mRNA.
  • To elucidate the mechanisms by which ICAM1 mRNA influences cellular processes independently of its protein product.
  • To investigate the implications of these findings in human cells and lung cancer.

Main Methods:

  • Utilized CRISPR-Cas9 for ICAM1 protein knockout and shRNA for RNA knockdown in human cells.
  • Employed overexpression of mutated ICAM1 mRNA and ICAM1 coding sequence (CDS) for validation.
  • Analyzed the formation of double-stranded RNA (dsRNA) from ICAM1/ICAM1-AS transcripts.
  • Investigated the interaction with interleukin enhancer binding factor 2 (ILF2)/ILF3 complex.
  • Performed clinical analysis of ICAM1/ICAM1-AS expression in lung cancer.

Main Results:

  • ICAM1 depletion via protein knockout and RNA knockdown yielded opposing effects on cell proliferation.
  • ICAM1/ICAM1-AS cis-antisense transcripts formed dsRNA, sequestering the ILF2/ILF3 complex.
  • This complex entrapment inhibited DNA binding in a length-dependent manner, suppressing EIF4E transcription and global protein synthesis.
  • Clinical data showed coordinated downregulation of ICAM1/ICAM1-AS in lung cancer, irrespective of ICAM1 protein levels.

Conclusions:

  • ICAM1 mRNA plays a regulatory role in cellular transcription through the dsRNA-ILF2/3 axis.
  • The study challenges the interpretation of gene silencing effects observed between RNA knockdown and protein knockout.
  • Findings underscore the significance of independent mRNA functions beyond translation.
Keywords:
ICAM1ILF2/ILF3 complexdsRNAlncRNAsnon-canonical mRNAs functiontranslation

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