How Are Genes Controlled

Question 1

Fat metabolism

Answer 1

(1) Fatty acid entry into cell
(2) Activation and transesterification (3) Mitochondrial uptake
(4) Formation of ketone bodies

Question 2

Symptoms of Medium chain Co-A dehydrogenase deficiency (MCADD)in babies

Answer 2

l poor feeding l drowsiness l sleepiness
l vomiting
l lethargy
l hyperglycemia l hepatomegaly l seizures
l Coma l Death

Question 3

Gene regulation in bacteria

Answer 3

-precursor-enzyme1-enzyme 2-enzyme 3-tryptophan
> feedback inhibition can affect the regulation of enzyme activity

Question 4

Allosteric:

Answer 4

A protein with a structure that is altered reversibly by a small molecule so that its original function is modified

Question 5

Operon model

Answer 5

Cluster of functionally relearned genes can be coordinately controlled by a single on-off switch

Question 6

Repressible operons

Answer 6

• The operon can be switched off by a protein repressor
• The repressor prevents gene transcription by binding to the operator and blocking RNA polymerase
• The repressor is the product of a separate regulatory gene, located some distance from the operon itself
• The repressor can be in an active or inactive form, depending on the presence of other molecules
• A corepressor is a molecule that cooperates with a repressor protein to switch an operon off

Question 7

Inducible operons

Answer 7

The lac operon is an inducible operon and contains genes that code for enzymes used in the hydrolysis and metabolism of lactose
• By itself, the lac repressor is active and switches the lac operon off
• A molecule called an inducer inactivates the repressor to turn the lac operon on

Question 8

Positive regulation

Answer 8

• Some operons are also subject to positive control through a stimulatory protein, such as cyclic AMP receptor protein (CRP), an activator of transcription

• When glucose (a preferred food source of E. coli) is scarce, CRP is activated by binding with cyclic AMP (cAMP)

-Activated CRP attaches to the promoter of the lac operon and increases the affinity of RNA polymerase, thus accelerating transcription

When glucose levels increase, CRP detaches from the lac operon, and transcription returns to a normal rate
• CRP helps regulate other operons that encode enzymes used in catabolic pathways

Question 9

Operons

Answer 9

• Inducible enzymes usually function in catabolic pathways; their synthesis is induced by a chemical signal
• Repressible enzymes usually function in anabolic pathways; their synthesis is repressed by high levels of the end product

Question 10

Regulatory genes

Answer 10

• MyoD is a “master regulatory gene” that encodes a transcription factor that commits the cell to becoming skeletal muscle
• Some target genes for MyoD (protein) encode additional muscle-specific transcription factors

Question 11

DNA to protein

Answer 11

-transcription
-RNA processing and splicing
-transport
-translation
-protein assembly

-Signal Causes chromatin modification(dna unpacking )
-Gene available for transcription
-transcription
-rna processing and splicing
-transport of mRNA from the nucleus to the cytoplasm
-mRNA in cytoplasm is degraded and becomes a polypeptide
-protein processing resulting in an active protein
-degradation of protein
-transport of protein to cellular destination(eg enzymatic activity or structural support)

Question 12

Regulation of Chromatin structure

Answer 12

• Genes within highly packed heterochromatin are usually not expressed
• Chromatin-modifyingenzymesprovideinitialcontrolof gene expression by making a region of DNA either more or less able to bind the transcription machinery

Question 13

Epigenetics

Answer 13

-DNA methylation=methyl groups affected to certain dna bases repress gene activity

-histone modification=Molecules that can attach to tails of proteins called histones,they alter tiger activity of the DNA wrapped around them

Question 14

How does acetylation and methylation affect regulation of chromatin structure

Answer 14

• acetylation=opens up the chromatin structure,
  thereby promoting the initiation of transcription
  -methylation=can condense chromatin,and reduce transcription

Question 15

Transcriptional activators

Answer 15

• An activator is a protein that binds to an enhancer and stimulates transcription of a gene
• Activators have two domains, one that binds DNA and a second that activates transcription
• Bound activators facilitate a sequence of protein-protein interactions that result in transcription of a given gene

Question 16

Combinatorial Control of Gene Activation

Answer 16

• A particular combination of control elements can activate transcription only when the appropriate activator proteins are present
• With only a dozen or so control elements, a large number of potential combinations is possible

Question 17

Rubinstein-Taybi syndrome (RST)

Answer 17

-caused by histone modification enzymes
-characteristics: short stature, moderate to severe intellectual disability,distinctive facial features, broad thumbs and first toes.
-can include:eye abnormalities,heart and kidney defects dental problems,Obesity,Increased risk of noncancerous brain and skin tumours.
- 1 in 100,000 to 125,000 new- borns.

-Autosomal dominant pattern
-Loss of function in
CREBBP or EP300 are the most common cause.
- Also linked to deletions in the short arm of chromosome 6.

Question 18

Chops syndrome

Answer 18

-caused by transcriptional elongation factor
- Extremely rare
- Autosomal dominant pattern
-Characteristics;
• Cognitive impairment,
• Coarse facial features
• Heart defects
• Obesity
• Pulmonary issues
• Short stature
• Skeletal abnormalities
-Caused by gain-of-function mutations in the ALF homology domain of AFF4 , which encodes a key component of the super elongation complex (SEC)
- Important during embryonic development
-The AFF4 protein is normally degraded by ubiquitination-dependent proteasomal degradation but these missense mutations hamper the binding of SIAH1, causing reduced degradation.

The AFF4 protein is normally degraded by ubiquitination-dependent proteasomal degradation but these missense mutations hamper the binding of SIAH1, causing reduced degradation.

Question 19

Spinal muscular atrophy Sma type 1

Answer 19

• SMA affects 1 in 8,000 to 10,000 people worldwide, with type 1 accounting for half of cases.
• Weak respiratory muscles and an abnormally bell-shaped chest.
• Difficulty feeding and swallowing
• Muscle weakness.
• Most individuals die of respiratory failure during early childhood.
• An autosomal recessive disorder.
• Caused by loss of function mutations in
survival of motor neuron 1 (SM1)
• Presentation can be modified due to copy number variation (CNV) in SM2
• Artificially enhancing SM2 production
• SM2 has a fault that results in the
skipping of exon 7.
• Nusinersen is an antisense oligonucleotide that acts as a splice- altering oligonucleotide.

Question 20

mRNA processing

Answer 20

• Nucleotide sequences that influence the life span of mRNA in eukaryotes reside in the untranslated regions (UTRs).
- Destabilizing elements (DEs) and Stabilizing elements (SEs) in the 3’UTR act as binding sites for specific RNA-binding proteins (RBPs)
that act to either reduce or increase the half-life of the RNA.
- 3’UTRs contain recognitions sites for microRNAs that are involved in the repression of mRNA translation and sometime their
degradation, through interaction with the RNA-induced silencing complex (RISC).

• The 5’UTR acts as an entry point for the ribosome and can adopt elaborate RNA secondary and tertiary structures that may regulate translation initiation in a cap-dependent or cap-independent manner

Poly(A)tail (~200bp) helps with nuclear export and translation
• 5’ CAP guanine is attached by 5’ to 5’ triphosphate linkage and methylated at N7 it helps with transport and RNA degradation

Question 21

Protein Degradation

Answer 21

• The length of time each protein functions is regulated by selective degradation.
• Cells mark proteins for degradation by attaching ubiquitin to the
• This mark is recognized by proteasomes, which recognize and degrade the proteins

• The length of time each protein functions is regulated by selective degradation
• Cells mark proteins for degradation by attaching ubiquitin to them
• This mark is recognized by proteasomes, which recognize and degrade the proteins

Question 22

Non-coding RNAs

Answer 22

• Not all RNA’s code for proteins
• For example, rRNA and tRNA

Question 23

Mirna

Answer 23

• MicroRNAs(miRNAs)aresmall,single-strandedRNA molecules that can bind complementary sequences in mRNA
• The miRNAs and associated proteins cause degradation of the target mRNA or sometimes block its translation
• Biologists estimate that expression of at least one- half of human genes may be regulated by miRNAs

Question 24

Sequence of miRNA

Answer 24

-it binds to mRNA
-if the bases are complementary,mRNA is degraded;if the match is less complete,translation is blocked

Question 25

Mature microRNAs (miRNAs)

Answer 25

guide Argonaute-containing complexes to target sites in mRNAs, usually in the 3’UTR, that are partially complementary to the miRNA sequence, and induce translational repression. This is called the micro RNA-induced Silencing Complex (miRISC).
•
Biologists estimate that expression of at least one-half of human genes may be regulated by miRNAs

Question 26

SiRNA

Answer 26

are similar to miRNAs in size and function

The blocking of gene expression by siRNAs is called RNA interference (RNAi)

Question 27

Piwi-interacting RNAs (piRNAs)

Answer 27

induce formation of heterochromatin, blocking the expression of parasitic DNA elements in the genome known as transposons
• piRNAs help to reestablish appropriate methylation patterns during gamete formation in many animal species
• Other non-coding RNAs are also involved in heterochromatin formation and regulation

Question 28

Compare siRNA to miRNA

Answer 28

-si is Double-stranded RNA that contains 30 to over 100bp whereas mi contains 70- 100bp with interspersed mismatches and hairpin structure

-si has 21-23 nucleotide RNA duplex with 2 nucleotides 3’overhang whereas 19-25 nucleotide RNA duplex with 2 nucleotides 3’overhang

-si is Fully complementary to mRNA whereas mi is Partially complementary to mRNA, typically targeting the 3’ untranslated region of mRNA
- si has one mRNA target whereas mi has multiple

-si mechanism for gene regulation includes Endonucleolytic cleavage of mRNA Whereas mi includes Translational repression Degradation of mRNA Endonucleolytic cleavage of mRNA (rare)