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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
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Variant Transcript of ROR1 ENST00000545203 Does Not Encode ROR1 Protein.

Jie Xian1, Navyaa Sinha1, Christina Girgis1

  • 1Center for Novel Therapeutics, Moores Cancer Center, Department of Medicine, University of California, San Diego, CA 92037, USA.

Biomedicines
|July 27, 2024
PubMed
Summary
This summary is machine-generated.

A variant transcript (ROR1) was previously thought to encode cytoplasmic ROR1 protein. However, this study demonstrates ROR1 lacks translation initiation, meaning it cannot produce protein and is not detected in cancers.

Keywords:
ROR1anti-ROR1 antibodyneoplasiavariant transcripts

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Area of Science:

  • Molecular biology
  • Cancer research
  • Bioinformatics

Background:

  • Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is implicated in cancer.
  • A variant transcript, ROR1, was proposed to encode a cytoplasmic ROR1 protein.
  • This variant was suggested to be predominant in neoplastic and normal cells.

Purpose of the Study:

  • To investigate the protein-coding potential of the ROR1 variant transcript.
  • To determine if ROR1 expression contributes to detectable ROR1 protein in cancer cells.

Main Methods:

  • Lentivirus vectors were generated to express full-length ROR1 or ROR1.
  • Cellular expression of ROR1 protein was analyzed via western blotting and flow cytometry.
  • Bioinformatic analysis of GTEx and TCGA datasets was performed.

Main Results:

  • Cells expressing ROR1 exhibited both surface and cytoplasmic ROR1 protein.
  • Cells expressing ROR1 showed neither surface nor cytoplasmic ROR1 protein.
  • ROR1 lacks an in-frame initiation codon, preventing its translation into protein.

Conclusions:

  • The ROR1 variant transcript cannot be translated into ROR1 protein.
  • Detection of ROR1 protein in cancers cannot be attributed to ROR1 expression.
  • Previous assumptions regarding ROR1's role in cancer protein detection are incorrect.