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Related Concept Videos

Leaky Scanning02:28

Leaky Scanning

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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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Initiation of Translation02:33

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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
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Translation01:31

Translation

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Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
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Ribosome Profiling02:24

Ribosome Profiling

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Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
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Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

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Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
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Related Experiment Video

Updated: Aug 28, 2025

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
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Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers.

Alec C Gleason1, Ghanashyam Ghadge1, Yoshifumi Sonobe1

  • 1Department of Neurology, University of Chicago Medical Center, Chicago, IL 60637, USA.

International Journal of Molecular Sciences
|September 23, 2022
PubMed
Summary
This summary is machine-generated.

Noncanonical translation initiation codons (TICs) upstream of main sites are often found in cancer-associated genes. These TICs, particularly in longer 5' untranslated regions (5'UTRs), can initiate the translation of oncogenic proteins.

Keywords:
cancercanonical and noncanonical translation initiation codonsoncogeneoncogenesisprotein translationtranslation initiationtumorigenesis

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Canonical and noncanonical translation initiation codons (TICs) upstream of main sites are implicated in oncogenic protein translation.
  • Previous studies reported conflicting data on nucleotide patterns surrounding noncanonical TICs.

Purpose of the Study:

  • To investigate the nucleotide sequences flanking noncanonical TICs.
  • To explore the relationship between 5' untranslated region (5'UTR) length and the utilization of upstream TICs in cancer-associated genes.

Main Methods:

  • Utilized ribosome profiling and mass spectroscopy to identify TICs.
  • Developed and applied a Kozak Similarity Score algorithm to analyze flanking nucleotide sequences.
  • Compared 5'UTR lengths of cancer-associated genes with upstream TICs to control genes.

Main Results:

  • Nearly all noncanonical TICs exhibit flanking nucleotides closely matching the Kozak sequence.
  • Flanking nucleotides of alternative noncanonical TICs often resemble the Kozak sequence more than those of canonical TICs.
  • Cancer-associated genes with upstream TICs possess significantly longer 5'UTRs compared to genes without upstream TICs.

Conclusions:

  • The Kozak sequence context favors the utilization of noncanonical TICs, even those in the 5'UTR.
  • Longer 5'UTRs may promote ribosome binding to upstream noncanonical TICs, contributing to oncogenic protein overexpression in cancer.
  • Noncanonical TICs, previously considered disadvantageous, may play a crucial role in cancer development by translating oncogenic proteins.