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    Lecture 5 - Translational Regulation

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    a192062
    This document summarizes key aspects of translational regulation, including the key players in protein synthesis like ribosomes and tRNAs. It describes the three phases of translation - initiation, elongation, and termination - with a focus on the initiation phase. Initiation involves regulatory elements in mRNA like the 5' cap and IRES that influence binding of initiation factors and ribosomes. Factors like eIF4E, mTOR signaling, and 4E-BPs regulate initiation through activation or repression. The document also discusses post-translational modifications like ubiquitination and the role of proteasomes in targeted protein degradation. Finally, it mentions how dysregulated translation can contribute to cancer and cutting-edge technologies like ribosome profiling and single-

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    Lecture 5 - Translational Regulation

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    a192062
    18 views20 pages
    This document summarizes key aspects of translational regulation, including the key players in protein synthesis like ribosomes and tRNAs. It describes the three phases of translation - initiation, elongation, and termination - with a focus on the initiation phase. Initiation involves regulatory elements in mRNA like the 5' cap and IRES that influence binding of initiation factors and ribosomes. Factors like eIF4E, mTOR signaling, and 4E-BPs regulate initiation through activation or repression. The document also discusses post-translational modifications like ubiquitination and the role of proteasomes in targeted protein degradation. Finally, it mentions how dysregulated translation can contribute to cancer and cutting-edge technologies like ribosome profiling and single-

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    translational regulation of gene

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    Lecture 5 - Translational regulation

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    This document summarizes key aspects of translational regulation, including the key players in protein synthesis like ribosomes and tRNAs. It describes the three phases of translation - initiation, elongation, and termination - with a focus on the initiation phase. Initiation involves regulatory elements in mRNA like the 5' cap and IRES that influence binding of initiation factors and ribosomes. Factors like eIF4E, mTOR signaling, and 4E-BPs regulate initiation through activation or repression. The document also discusses post-translational modifications like ubiquitination and the role of proteasomes in targeted protein degradation. Finally, it mentions how dysregulated translation can contribute to cancer and cutting-edge technologies like ribosome profiling and single-

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    18 views20 pages

    Lecture 5 - Translational Regulation

    Uploaded by

    a192062
    This document summarizes key aspects of translational regulation, including the key players in protein synthesis like ribosomes and tRNAs. It describes the three phases of translation - initiation, elongation, and termination - with a focus on the initiation phase. Initiation involves regulatory elements in mRNA like the 5' cap and IRES that influence binding of initiation factors and ribosomes. Factors like eIF4E, mTOR signaling, and 4E-BPs regulate initiation through activation or repression. The document also discusses post-translational modifications like ubiquitination and the role of proteasomes in targeted protein degradation. Finally, it mentions how dysregulated translation can contribute to cancer and cutting-edge technologies like ribosome profiling and single-

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    STBP2022: Gene expression

    Translational regulation

    Jasper James PhD

    Jabatan Sains Biologi & Bioteknologi


    FST UKM
    Outline
    Translational regulation
    • Key players
    • Initiation activation &
    repression
    • PTMs
    Protein synthesis
    a.k.a translation
    • ______ is translated by moving through ribosome, a multicomponent
    entity, composed of RNAs and proteins.
    • Ribosome is organized in two subunits: A 40S (________) and a 60S
    (______) subunit.
    • 40S – decodes genetic info, 60S – catalyzes peptide formation.
    Protein synthesis
    Initiation

    Elongation

    Termination
    Regulation of translation

    The key players


    • Ribosomes: facilitate protein synthesis
    • tRNA: transport amino acids to the ___________
    • mRNA: carries genetic info from DNA to the ____________
    Initiation
    Regulatory elements in mRNA
    5’ UTR – influence translation efficiency
    • Variations in length and sequence affects the
    binding of ______________ (IF) and ribosomes –
    thus modulating the rate of ____________

    Internal Ribosome Entry Sites (IRES) – RNA sequences


    within mRNA , initiation independent of 5’ cap (by-
    pass)
    • provide an alternative mechanism for translation
    initiation, ensuring ____________________ under
    conditions where traditional cap-dependent initiation
    may be hindered
    Initiation
    Activation
    elF4E – key component of elF4F complex
    • Binds to the 5’ cap and facilitate recruitment of
    ribosome and other IF
    • Its abundance promotes protein synthesis

    mTOR (Mechanistic Target of Rapamycin) Signaling –


    central regulator of cellular processess
    • Promotes phosphorylation of downstream effectors
    • Enhances translation by providing favorable
    conditions
    Initiation
    Repression
    elF4E-binding proteins (4E-BPs) – a regulatory
    protein
    • Binds and inhibits elF4E preventing association
    with 5’ cap
    • Phosphorylation of 4E-BPs alleviates
    translational repression

    RNAi – RISC
    • Still remember? Leads to mRNA degradation by
    cellular ___________
    Post-translational modification (PTMs)

    Protein Processing and Degradation

    • After translation, various types of


    protein processing, including
    cleavage and the addition of
    chemical groups, are subject to
    control
    Post-translational modification (PTMs)
    Post-translational modification (PTMs)
    Protein degradation
    • Lifespan of protein is strictly regulated
    • Marked protein for destruction is attached by a
    small protein ubiquitin

    • Protein complexes - proteasomes

    Proteasomes are
    giant protein
    complexes that bind
    protein molecules
    and degrade them
    Ubiquitination
    Proteasome
    Ubiquitin and ubiquitin
    Proteasome to be recycled

    Protein to Ubiquitinated Protein


    be degraded protein fragments
    Protein entering
    (peptides)
    a proteasome
    Dysregulated translation and cancer
    • The role of mRNA translation – further reading
    https://doi.org/10.1016/j.trecan.2020.09.005
    Cutting-edge technologies • Ribosome Profiling:
    allows scientists to
    examine the locations of
    ribosomes on mRNAs at
    a genome-wide scale,
    providing insights into
    translational dynamics.

    • Single-Cell Analysis:
    Single-cell RNA
    sequencing enable us to
    study translational
    heterogeneity among
    individual cells within a
    population.
    Next lecture:

    Epigenetic regulation
    THANK YOU!

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