Molecular Mechanisms of Disease
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Questions and Answers

What is the function of the nuclear pore complex?

The nuclear pore complex is a gateway that controls the passage of molecules between the nucleus and the cytoplasm. It allows for the transport of RNA products for translation and proteins needed for transcription into the nucleus.

What are some of the key components of a transcription factor?

  • DNA-binding domain/motif (correct)
  • Activation domain (correct)
  • Dimerization domain (correct)
  • All of the above

What are the three main types of DNA-binding motifs?

  • Zinc fingers (correct)
  • Helix-Loop-Helix (HLH) (correct)
  • Leucine Zipper (correct)
  • All of the above

What is the function of the mediator complex in gene regulation?

<p>The mediator complex acts as a bridge between transcription factors and RNA polymerase II, helping to control gene expression. It also plays a role in chromatin remodeling and other regulatory processes.</p> Signup and view all the answers

What is the role of co-activators in gene regulation?

<p>Co-activators are proteins that enhance gene expression by interacting with transcription factors or by directly altering chromatin structure. They do not directly bind to DNA.</p> Signup and view all the answers

What is the function of histone acetyltransferases (HATs) in gene regulation?

<p>HATs add acetyl groups to lysine residues on histone proteins, which loosens chromatin structure and increases gene expression. This makes DNA more accessible to transcription factors.</p> Signup and view all the answers

What is the function of chromatin remodeling complexes?

<p>Chromatin remodeling complexes like SWI/SNF can alter chromatin structure by repositioning histones, making DNA more accessible to transcription factors and altering the accessibility of genes.</p> Signup and view all the answers

Only processed mRNA is allowed to leave the nucleus and enter the cytoplasm for translation.

<p>True (A)</p> Signup and view all the answers

What are the two major classes of proteins that regulate splicing?

<p>Both A and B (C)</p> Signup and view all the answers

How does the phosphorylation of elF2 affect translation?

<p>Phosphorylation of elF2 inhibits translation by preventing the exchange of GDP for GTP. This occurs during stress conditions, such as heat shock or viral infection.</p> Signup and view all the answers

What is the role of the 5' and 3' untranslated regions (UTRs) of mRNA in translation?

<p>The 5' and 3' UTRs of mRNA contain regulatory sequences for several stages of translation, including initiation, localization, stability, and degradation.</p> Signup and view all the answers

How does an iron regulatory protein (IRP) regulate ferritin mRNA translation?

<p>When iron levels are low, IRP binds to the iron-response element (IRE) in the 5' UTR of ferritin mRNA, preventing translation. When iron levels are high, IRP dissociates from the IRE allowing translation to proceed.</p> Signup and view all the answers

What are the two major mechanisms by which microRNAs (miRNAs) regulate gene expression?

<p>All of the above (D)</p> Signup and view all the answers

What is the function of the proteasome?

<p>The proteasome is a protein-degrading machine that removes damaged or unwanted proteins from the cell. It is found in both the nucleus and cytoplasm.</p> Signup and view all the answers

What is the role of ubiquitin ligases in protein degradation?

<p>Ubiquitin ligases attach ubiquitin molecules to targeted proteins, marking them for degradation by the proteasome. They play a critical role in recognizing and tagging proteins for breakdown.</p> Signup and view all the answers

Flashcards

Nuclear Localization Signal (NLS)

Specific amino acid sequence on a protein that directs its transport into the nucleus.

Nuclear Export Signal (NES)

Specific amino acid sequence on a protein that directs its transport out of the nucleus.

Importins

Nuclear transport receptors that bind to NLS sequences and ferry proteins into the nucleus.

Exportins

Nuclear transport receptors that bind to NES sequences and shuttle proteins out of the nucleus.

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RanGTP

A protein involved in nuclear transport, changing conformation and influencing importin and exportin function.

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Nuclear Pore Complex (NPC)

Complex structure that allows passage of molecules between the nucleus and cytoplasm.

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Transcription Factors (TF)

Proteins that bind specific DNA sequences and regulate gene expression.

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General Transcription Factors

Transcription factors that bind to the core promoter region of genes, aiding RNA polymerase's binding.

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Sequence-Specific Transcription Factors

Transcription factors that bind to regulatory elements outside of the core promoter, influencing transcription levels.

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Activators

Transcription factors that increase gene expression.

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Repressors

Transcription factors that decrease gene expression.

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Enhancer sites

DNA regions far from a gene that can dramatically increase transcription.

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Co-activators

Proteins that increase gene expression but don't directly bind DNA.

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Mediator complex

A large protein complex that acts as a bridge between transcription factors and RNA polymerase.

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Histone acetyltransferases (HATs)

Enzymes that add acetyl groups to histone tails, increasing chromatin accessibility.

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Chromatin remodeling complexes

Enzymes that reposition or modify nucleosomes, affecting gene expression.

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mRNA processing

Modifications to RNA transcripts (pre-mRNA) before they enter the cytoplasm as a functional mRNA molecule

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Splicing

Removal of introns and joining of exons in pre-mRNA.

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SR proteins

Proteins that bind to mRNA to regulate splicing.

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hnRNPs

Proteins that bind to mRNA to regulate splicing.

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Translational control

Regulation of protein synthesis at the level of translation.

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5' and 3' UTRs

Untranslated regions at the 5' and 3' ends of an mRNA molecule.

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MicroRNAs (miRNAs)

Small RNA molecules that can bind to mRNAs to regulate their stability or translation.

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mRNA stability

Regulation of how long mRNA molecules persist in the cytoplasm.

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Study Notes

Molecular Mechanisms of Disease

  • The cell diagram shows the various cellular components and their functions in a comprehensive manner.
  • The nucleus, depicted in the diagrams and text, is the site of transcription, containing tightly packed DNA and protein complexes (chromatin).
  • The nucleolus, a structure within the nucleus, is also highlighted.
  • Proteins required for transcription and RNA products for translation are transported in and out of the nucleus, respectively.
  • Transport occurs through the nuclear pores of the nuclear envelope.
  • Cellular components are named.
  • The nuclear membrane, consisting of the outer and inner nuclear membranes, is continuous with the ER, with a lamina providing mechanical support and chromatin anchoring.
  • Approximately 60 transmembrane proteins like Nesprin 1/2 and 3 assist anchoring.
  • There are over 1000 nuclear pore complexes.
  • The nuclear pore complex (NPC) comprises ~30 nucleoporins and acts as a gateway for RNA and protein transport across the nuclear envelope.
  • The NPC has an octagonal symmetry and a central channel (20-40 nm in diameter).
  • The nucleoporins lining the central channel have a FG domain for forming a hydrophobic mesh that blocks free diffusion of large macromolecules.
  • Proteins for transport contain specific amino acid sequences, including Nuclear Localization Signal (NLS) and Nuclear Export Signal (NES).
  • Transport receptors (importins and exportins) ferry proteins across the envelope.
  • Exportins and RanGTP proteins bind to NES sequences.
  • mRNAs are transported in the cell as ribonucleoproteins (RNPs).
  • Associated proteins interact with FG domain nucleoporins.
  • Only mature (fully processed) mRNAs are exported and this is dependent on Nxf1 and Nxt1.
  • mRNA does not need an export protein or RanGTP to be transported.
  • Four levels of gene regulation: Transcriptional, Processing, Translational, and Posttranslational control.
  • Transcriptional control involves general transcription factors (like TBP, TAF, and TFIIA-H), and sequence-specific transcription factors (activators and repressors).
  • Transcription factors bind to regulatory DNA sites to either stimulate or repress transcription.
  • Transcription factors (TF) have basic structures where DNA-binding motifs bind to specific DNA sequences.
  • There are three major types of DNA-binding motifs: Zinc fingers, Helix-Loop-Helix (HLH), and Leucine Zipper.
  • The DNA sites for TF binding include response elements in the core promoter, enhancer sites, and proximal and distal promoter regulatory sequences (e.g., CAAT box, GC box).
  • Co-activators (proteins that increase gene expression without directly binding DNA) act in two ways: direct interactions with the PIC (pre-initiation complex), and interactions with chromatin.
  • Histone acetyltransferases (HATs) transfer acetyl groups to histones, reducing their positive charge and exposing binding sites for chromatin remodeling complexes such as SWI/SNF.
  • Translational control, after mRNA leaves the nucleus, involves mechanisms like initiation and progression of translation, localization of mRNAs to specific cell regions, and mRNA stability within the cytoplasm.
  • Global regulation of translation affects all mRNAs and involves phosphorylation and dephosphorylation of initiation factors (e.g., elF2).
  • Specific regulation of translation occurs via regulatory sequences in the 5' and 3' untranslated regions (UTRs) of mRNA and includes regulatory proteins (e.g., iron regulatory proteins) which bind to the UTR.
  • RNA interference (RNAi) uses small interfering RNAs (siRNAs) or microRNAs (miRNAs) to inhibit gene expression by degrading or inhibiting translation of target mRNA.

Overview of Gene Regulation

  • In the diagram, various levels of transcript regulation are shown, including transcriptional control.
  • Levels of gene regulation include transcriptional control, post-translational control, processing, and translational control.
  • Transcription begins with nascent RNAs from genes.

Next Lecture

  • The next lecture is on Wednesday at 2:30 pm about Epigenetics (Gene-Environment Interactions).

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HSS2305C Fall 2024 Lecture 11 PDF

Description

Explore the intricate details of cellular components and their functions in disease mechanisms. This quiz delves into the structure and operation of the nucleus, nucleolus, and nuclear pores, highlighting key proteins and complexes involved in transcription and translation. Enhance your understanding of how these elements contribute to cellular function and pathology.

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