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Related Concept Videos

Initiation of Translation02:33

Initiation of Translation

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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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Leaky Scanning02:28

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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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Regulated mRNA Transport02:22

Regulated mRNA Transport

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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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Regulated mRNA Transport02:22

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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...
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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
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Global mRNA selection mechanisms for translation initiation.

Joseph Costello, Lydia M Castelli, William Rowe

    Genome Biology
    |February 5, 2015
    PubMed
    Summary

    mRNA translation initiation is complex, with the closed loop complex regulating some mRNAs. Other mRNAs rely on Pab1p independently, and 4E-BPs self-regulate their own translation.

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    Area of Science:

    • Molecular Biology
    • Yeast Genetics
    • Translational Control

    Background:

    • mRNA selection for translation initiation is poorly understood.
    • The closed loop complex (eIF4E, eIF4G, PABP) and 4E-BP regulation are key players.
    • Investigating these mechanisms across the yeast transcriptome is crucial.

    Purpose of the Study:

    • To evaluate the role of the closed loop complex in gene regulation.
    • To understand 4E-BP regulation across the yeast transcriptome.
    • To elucidate mRNA selection mechanisms for translation initiation.

    Main Methods:

    • RNA immunoprecipitation followed by sequencing (RIP-seq) was employed.
    • Analysis of the entire yeast transcriptome was performed.
    • Correlation analysis between protein interaction and translation levels.

    Main Results:

    • Distinct mRNA populations identified: one enriched with closed loop components (e.g., ribosomal protein mRNAs), another with limited closed loop interaction but high Pab1p interaction.
    • Pab1p interaction strongly correlates with translation levels, suggesting a closed loop-independent role.
    • 4E-BPs were found to self-regulate by inhibiting the translation of their own mRNAs.

    Conclusions:

    • mRNA selection for translation is not uniformly regulated.
    • While the closed loop complex is vital for many mRNAs, alternative mechanisms (potentially Pab1p-dependent) facilitate ribosome loading for others.
    • A novel self-regulatory circuit for yeast 4E-BPs was characterized.