Cycle 8 (Reg Control)

Question 1

Transcriptional Regulation

What does transcriptional regulation do?

Answer 1

Determines which genes are transcribed

Question 2

Transcriptional Regulation

Explain in depth the function of enhancers

Answer 2

• Transcriptional factors bind to promoter proximal and make the promoter more attractive/improve transcription
  
  • But they keep falling off
• Upstream, enhancers has proteins bound to it that stabilises the transcription factors and holds them together (sandwich) using a coactivator
  
  • Silencers (like enhancers) stabilise repressors at the promoter

Question 3

Transcriptional Regulation

Define combinatorial gene regulation

Answer 3

The activator proteins that bind to the promoter or enhancer can exist in different combinations in different tissues. Liver, for example, only wants gene B, so it uses 1, 5, 8, and 11 activators.

This is combinatorial gene regulation​: the combining of a few regulatory proteins in particular ways so that the transcription of a wide array of genes can be controlled and a large number of cell types can be specified.

Question 4

Transcriptional Regulation

Explain the idea of coordinated regulation

Answer 4

Genes with related functions can be regulated together because they share a regulatory sequence

• Ex. steroid hormone​ enters cell, binds with steroid hormone receptor to form a complex, which enters nucleus and binds to steroid hormone response element, activating transcription of multiple genes

Question 5

Transcriptional Regulation

Explain DNA methylation

Answer 5

Enzymes add a methyl group directly onto DNA, which attracts HDAC (histone deacetylase) –> makes the chromatin more tighly packed and gene expression drops

• Also decreases transcription by itself (methyl group addition only)

Question 6

Transcriptional Regulation

Explain how chromosome structure acts as transcriptional control

Answer 6

• DNA wraps around histones → forms nucleosome → organizes DNA into chromatin
• The promoter is inactive in this state because nucleosomes prevent transcriptional factors from binding
• Acetyl groups can be added which changes charge of histone tails and loosens interaction with DNA, enabling transcription

Question 7

Posttranscriptional Regulation

What does posttranscriptional regulation do?

Answer 7

Determines the types and availability of mRNAs to ribosomes

Question 8

Posttranscriptional Regulation

Explain splicing and alternative splicing

Answer 8

• Splicing refers to the removal of introns via spliceosomes
• Spliceosomes are aggregates of snRNPs (small ribonuclear protein) which have snRNA proteins inside that pair with themselves
• Some of the snRNAs also pair with the mRNA at the splice signal

Alternative splicing

1. Whether or not an intron is removed is a choice
2. Whether sequences are considered intron or exon depends on the tissue
3. This allows for protein diversity → organism complexity; one gene could have thousands of protein products

Question 9

Posttranscriptional Regulation

What are masking proteins?

Answer 9

Masking proteins​ bind to mRNAs and make them unavailable for protein synthesis (ex., keeping mRNAs in an inactive form of an egg until fertilized)

Question 10

Posttranscriptional Regulation

Explain mRNA breakdown control

Answer 10

The mRNA breakdown mechanism involves a regulatory molecule, such as a steroid hormone, directly or indirectly affecting the mRNA breakdown steps, by either slowing or increasing the rate of those steps.

5’UTR regions are important for determining mRNA half-life

Question 11

Posttranscriptional Regulation

Explain RNA interference (RNAi):​ miRNA

Answer 11

• BINDS TO 3’UTR of target mRNA
• miRNA transcript is looped into hairpin structure creating double strands, pre-miRNA leaves nucleus and a dicer enzyme​ removes the loop, then a protein complex removes one of the double strands
• miRNA binds to RNA that has a complementary or nearly complementary segment

1. Imperfect pairing of miRNA to target mRNA causes blockage of translation
2. Perfect pairing causes mRNA degradation

Question 12

Posttranscriptional Regulation

Explain RNA interference (RNAi):​ siRNA

Answer 12

siRNAs are produced from double-stranded RNA not encoded by nuclear genes (ex., viruses)

• Replication cycle of many viruses with RNA genomes involves d-s RNA –> cells attacked by such a virus can defend themselves using siRNA that they produce from the virus’s own RNA

Question 13

What does translational regulation do?

Answer 13

Determines rate at which proteins are made

Question 14

State the main mechanism of translational regulation

Answer 14

One important mechanism for translational regulation involves adjusting the length of the poly(A) tail of the mRNA

• Increases in poly(A) tail length result in increased translation; decreases in length result in decreased translation.

Question 15

What does posttranslational regulation do?

Answer 15

Determines the availability of finished proteins

Question 16

Explain the 3 mechanisms of posttranslational regulation

Answer 16

1. Chemical modification​: addition or removal of chemical groups that alter protein activity
2. Processing​: proteins are synthesized as inactive precursors, which are converted to an active form under regulatory control (ex., pepsinogen is the inactive precursor of pepsin which is activated by removal of amino acids)
3. Degradation​: short-lived proteins have a “doom tag” consisting of a protein called ubiquitin which allows protein to be recognized by proteasomes
   
   • Proteasome unfolds protein → enzymes in cytoplasmic complex digest protein into small peptides → released peptides are digested into amino acids by cytosolic enzyme