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Leaky Scanning

Leaky Scanning

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...

Initiation of Translation

Initiation of Translation

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...

The Unfolded Protein Response

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...

Regulation of the Unfolded Protein Response

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

Regulation of Expression at Multiple Steps

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...

Regulation of Expression Occurs at Multiple Steps

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...

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Related Experiment Video

Updated: Jun 29, 2025

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

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

Published on: May 1, 2020

Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding.

Ezgi Hacisuleyman¹, Caryn R Hale^2,3, Natalie Noble²

¹Laboratory of Molecular Neuro-oncology, The Rockefeller University, New York, NY, USA. fhacisuley@rockefeller.edu.

Nature Neuroscience

|April 8, 2024

Summary

This summary is machine-generated.

Neurons rapidly change protein expression during learning. Activity-dependent translation of upstream open reading frames (uORFs) by eIF4G2 controls local protein synthesis, linking neuronal activity to dendritic remodeling.

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Last Updated: Jun 29, 2025

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

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Published on: May 1, 2020

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Quantitative Immunofluorescence to Measure Global Localized Translation

Quantitative Immunofluorescence to Measure Global Localized Translation

Published on: August 22, 2017

Area of Science:

Neuroscience
Molecular Biology
Cell Biology

Background:

Learning and memory depend on activity-induced changes in dendritic translation.
The specific mRNAs involved and their regulatory mechanisms remain largely unknown.

Purpose of the Study:

To investigate how neuronal depolarization impacts local dendritic biology.
To identify mRNAs and proteins regulated by neuronal activity in dendrites.

Main Methods:

Dendritically targeted proximity labeling followed by crosslinking immunoprecipitation.
Ribosome profiling and mass spectrometry were employed to analyze translational changes.
Primary cortical neurons were depolarized using KCl or DHPG.

Main Results:

Neuronal depolarization rapidly reprogrammed dendritic protein expression, with weak correlation between mRNA and protein changes.
Depolarization enhanced translation of upstream open reading frames (uORFs) and downstream sequences for specific mRNAs.
This process involved phosphorylation and recruitment of the translation initiation factor eIF4G2, enabling localized protein synthesis.

Conclusions:

Activity-dependent translation of uORFs by eIF4G2 is a key mechanism coupling neuronal activity to local dendritic remodeling.
This pathway regulates the production of proteins crucial for long-term potentiation, cell signaling, and energy metabolism.