Exam 4: Transcription & RNA processing Flashcards

1
Q

Transcription

A

synthesis of RNA molecules that are complementary in sequence to a DNA template

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2
Q

RNA is different from DNA because

A

it contains ribose, it uses uracil to pair with adenine, it is single stranded

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3
Q

RNA polymerase

A

unwinds template DNA & creates RNA in 5’ to 3’ direction

Initiate RNA synthesis without a primer & more prone to error than DNA polymerase

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4
Q

RNA polymerase I

A

synthesizes ribosomal RNA (rRNA), which is a component of ribosome required for protein synthesis

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5
Q

RNA polymerase III

A

synthesizes tRNA - then chemically modified to make mature tRNA

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6
Q

RNA polymerase II

A

transcribes mRNA

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7
Q

Promoter

A

start of transcription

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8
Q

Terminator

A

end point of transcription

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9
Q

General transcription factors

A

essential to allow initiation of transcription of genes by Pol II - help Pol II recognize and bind to promotors
Basal transcription complex - initiating transcription only at low rate

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10
Q

TFIID (transcription factor for Pol II)

A

general transcription factor

complex of several proteins, contains TBP - binds to TATA box

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11
Q

TATA box

A

DNA sequence area in promotor region - always found in genes transcribed by Pol II
Acts as a binding site for general transcription factor, needed for binding of Pol II

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12
Q

TBP (TATA binding protein)

A

part of TFIID; binds to TATA box
Distorts DNA and directs other components of general transcription complex & Pol II to promoter - formation of transcriptional initiation complex

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13
Q

High rates of transcriptional initiation require

A

additional factors bound to other DNA sequences - GC-rich sequences (bind transcription factor SP-1) & CAAT box (binds transcription factor NF1) & enhancer elements (located further upstream of the promoter)

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14
Q

Actively transcribed regions of genome are more

A

Relaxed than inactive regions

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15
Q

Death cap mushroom (Amanita phalloides)

A

extremely poisonous fungus
contains toxin alpha-amanitin - inhibitor of Poll II (blocks synthesis of mRNA)
Results in massive liver failure - mRNA degraded during metabolism
No antidote

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16
Q

Rifampicin

A

antibiotic, inhibitor of RNA polymerase found in bacteria

Eukaryotic Pol II is unaffected - selectively kill bacteria (antibiotic against Mycobacterium tuberculosis)

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17
Q

Capping

A

RNA processing modification at 5’ end of pre-mRNA
“Cap” structure allows cell to distinguish mRNA molecules
Important for further processing & export

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18
Q

Splicing

A

in order to form mature mRNA the introns must be removed from the pre-mRNA & exons join together

19
Q

spliceosomes

A

catalyze pre-mRNA splicing

recognize boundaries between exons and introns

20
Q

differential (alternate) splicing

A

a pre-mRNA molecule may contain multiple exons, different subsets of which may be spliced together generating different mRNA molecules
Gives rise to tissue-specific isoforms of enzymes and other proteins

21
Q

Polyadenylation

A

3’ end of RNA specified by DNA signal - polyadenylation signal
transcribed into RNA & recognized by specific protein factors - cleaves RNA molecule and adds “tail” of around 200 adenine nucleotides - poly-A tail

22
Q

Ribonucleases

A

degrade mRNA molecule from both ends - first shortening of poly-A tail, which triggers removal of 5’ cap

23
Q

beta-thalassemia

A

results from reduced synthesis of beta-chain of hemoglobin

reduces amount of hemoglobin that can be formed = profound anemia

24
Q

Phenylketonuria (PKU)

A

inability to convert phenylalanine to tyrosine
due to mutation in phenylalanine hydroxylase gene - single base change in 5’ splice donor site of one particular intron
Incorrectly spliced mRNA and truncated protein that lacks one exon

25
Q

Chromatin remodeling complexes

A

use energy of ATP hydrolysis to change structure of nucleosomes so DNA becomes less tightly bound to histone core

26
Q

Histone acetyltransferases (HATs)

A

acetylate lysine residues in histones
reduces net positive charge of histones & decreases strength of their interaction w/ DNA (negatively charged)
histones located in regions of DNA that are actively transcribed are typically hyperacetylated

27
Q

histone deacetylases (HDACs)

A

catalyze removal of acetyl groups from histone & promote chromatin condensation
inhibit transcription
recruited to methylated DNA

28
Q

DNA methylation

A

tends to be found in transcriptionally silent regions

29
Q

Helix-turn-helix proteins

A

gene regulatory proteins
alpha-helices connected by short chain of amino acids
side chains of amino acids in more C-terminal of the two alpha-helices play an important role in DNA binding
homeobox proteins

30
Q

Zinc finger proteins

A

gene regulatory protein
zinc is required for protein folding and function
alpha-helix makes contact with the major groove of DNA
glucocorticoid receptor

31
Q

Leucine zipper proteins

A

gene regulation protein
dimers in which two alpha-helices join together to form a short coiled coil
contains hydrophobic residue, typically leucine, at every 7th position = hydrophobic residues down one side
positively-charged region interacts with DNA major groove
Fos and Jun

32
Q

DNA binding proteins

A

act as nucleation sites - recruit more proteins

33
Q

LDL receptor gene

A

responds to low cellular cholesterol
increased transcription of LDL receptor gene - results in increased production of LDL receptor protein and enhanced cholesterol uptake from blood

34
Q

SRE-1 (sterol responsive element-1)

A

gene specific regulatory sequence, transcription is regulated in response to cholesterol levels

35
Q

SP-1

A

transcription factor binds to GC boxes
zinc finger containing protein
help with assembly of Pol II
requires CRSP (cofactor required for SP-1 activation)
necessary but not sufficient for LDL receptor gene activation

36
Q

SREBP-1a

A

leucine zipper protein that binds to SRE-1
enters nucleus when cholesterol levels fall
when bound to SRE-1 recruits HAT - relaxes chromatin & allows for LDL receptor gene transcription (as well as other genes involved in metabolism of fatty acids & cholesterol)

37
Q

Binding of cortisol to glucocorticoid receptor

A

causes conformational change - frees receptor of associated proteins and exposes DNA-binding domain
allows uptake of hormone/receptor complex into nucleus
In nucleus binds to DNA at site called GRE (glucocorticoid responsive element) - enhancer element

38
Q

GRE

A

enhancer element - enhances transcription

can act at a distance and found upstream, downstream, or in middle of gene it regulates

39
Q

thyroid hormone receptors/RXR (retinoid X receptor) complex

A

found always in nucleus, bound to regulatory DNA sequences
absence of bound thryoid hormone, receptors repress transcription by recruiting HDAC activity - chromatin in condensed state
thyroid hormone binds, conformation change happens - displacement of HDAC and binding of HAT - relaxation of chromatin and transcription

40
Q

Rubinstein-Taybi syndrome

A

intellectual disability caused by point mutations, small deletions, and rearrangements within genes encoding CBP & EP300 (which facilitate transcription of PEPCK (phosphoenolypyruvate carboxykinase) as activated by gulcagon - elevated cAMP/PKA)

41
Q

CREB

A

PKA phosphorylates CREB, which binds to CRE promotor elements and recruits protein CBP (CREB binding protein)

42
Q

CBP

A

CREB binding protein binds to phosphorylated CREB at CRE region of DNA - recruits EP300 = transcription of PEPCK gene

43
Q

Estrogen

A

triggers proliferation in many breast cancers - estrogen receptor binds to DNA and recruits additional protein factors that activate transcription of estrogen-sensitive genes

44
Q

Tamoxifen

A

competitive inhibitor of estrogen receptor
can be used to inhibit tumor growth in breast cancer
Tamoxifen/receptor complex binds to DNA still, but doesn’t recruit additional factors needed to activate transcription