Eukaryotic Gene Expression 2

Gene Regulation by MicroRNAs and SiRNAs

  • MicroRNAs (miRNAs)

    • Endogenous molecules produced in the cell.

    • Single-stranded and not perfect matches to mRNA.

    • Involved in the regulation of gene expression and stop translation of target mRNAs.

    • Targeting is broad; can affect multiple sequences due to their imperfect matching.

  • Short Interfering RNAs (siRNAs)

    • Require perfect base pairing with their target mRNA.

    • More specific than miRNAs, targeting specific gene sequences.

    • Commonly used in therapeutic applications to silence viral mRNA, reducing disease-related proteins.

  • Protein Dicer

    • Enzyme that processes precursor double-stranded RNA (dsRNA) into short segments of miRNAs and siRNAs (approximately 21 nucleotides long).

RNA-Induced Silencing Complex (RISC)

  • Formation of RISC

    • Short dsRNA binds to an Argonaute protein, forming RISC.

    • Only the guide strand of RNA remains bound to Argonaute & directs the RISC to target mRNAs.

  • SiRNA Functionality

    • Perfectly complementary to target mRNA, leading to catalytic cleavage and degradation.

  • MicroRNA Functionality

    • Partially matches target mRNA, leading to inhibition of translation or degradation of mRNA.

    • Can target hundreds of mRNAs due to seed pairing.

Post-Translational Regulation

  • Introduction

    • Regulation occurs after mRNA is translated into a polypeptide chain.

  • Phosphorylation Effects

    • Phosphorylation of ribosomal components can prevent complex assembly and thus translation.

    • Often observed in neurological diseases like Alzheimer’s where protein synthesis is impacted.

  • Chemical Modifications

    • Various groups (e.g., methyl, phosphate, acetyl, ubiquitin) can be added or removed from proteins, affecting their activity.

    • Addition of a phosphate can activate a protein, while methylation can inactivate it.

    • Modifications occur in response to external stimuli (stress, nutrient availability, etc.).

Protein Degradation

  • Regulating Protein Availability

    • After proteins are created, they may need to be degraded or recycled.

    • Essential for cellular function and maintaining homeostasis.

Wrap-Up and Discussion

  • Review of the entire process from DNA regulation to protein synthesis and degradation.

  • Engagement activity: March Mammal Madness with a hypothetical discussion involving grizzly bears vs. pack of wolves.

    • Evidence-based analysis based on ecological interactions and statistics regarding grizzly and wolf encounters.

  • Emphasis on participation in the March Mammal Madness as a fun educational activity.