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Block Two Cell Bio > Transcription and RNA I > Flashcards

Transcription and RNA I Flashcards

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1
Q

Transcription

A

RNA synthesized using a DNA template, allows structural regulatory and translational info in DNA to be transferred to RNA where it can function throughout the cell

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2
Q

transcription as a process

A

transcriptional machinery localizes to specific sites in the nucleus (transcription factories) and it is accompanied by rapid changes in chromatin

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3
Q

mutations that alter transcription

A

associated with cancer, diabetes, developmental defects, autoimmune, neurological and cardiovascular diseases; most known are located within protein coding genes

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4
Q

cancer development

A

many cancer promoting oncogenes are transcription factors, alterations in transcription brought about by DNA methylation and histone modification patterns also associated

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5
Q

non-coding region

A

hundreds of thousands of potential transcriptional regulatory sequences located at non-coding regions some likely effect gene expression and potentially promote disease

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6
Q

transcription of protein coding genes

A

consists of 4 major phases

  1. Initiation
  2. Pausing
  3. Elongation
  4. Termination
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7
Q

RNA polymerase

A

3 types
RNA pol 1
RNA pol 2
RNA pol 3

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8
Q

RNA pol 1

A

RNA pol 1 -> Pre-rRNA -> rRNA

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9
Q

RNA pol 2

A

RNA pol 2 -> Pre- mRNA -> mRNA

RNA pol 2 -> ncRNA

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10
Q

RNA pol 3

A

RNA pol 3 -> pre-tRNA -> tRNA
RNA pol 3 -> pre-rRNA -> rRNA
RNA pol 3 -> small ncRNA

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11
Q

Ubiquitous constitutive genes

A

transcription factors and transcriptional machinery needed to transcribe these genes always present and active “house keeping genes”

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12
Q

Ubiquitious inducible genes

A

transcribed because transcription factors needed to transcribe them are activated in response to an inducing event

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13
Q

Cell type specific constitutive gene

A

Only expressed in specialized cells, but transcription factors and transcriptional machinery needed to transcribe these genes always present and active in those cells

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14
Q

Cell type specific inducible genes

A

only expressed in specialized cells when transcription factors needed to transcribe them are activated in response to inducing event

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15
Q

Constitutive vs inducible genes

A

constitutive always on inducible have to be turned on by inducing event

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16
Q

Major transcriptional regulators

A

DNA, nucleosomes, transcription factors, transcriptional coregulators, chromatin modifiers, RNA polymerase II preinitiation complex

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17
Q

Cataracts inheritability

A

TF heat shock factor 4 (HSF4) mutation which reduces level of the protein; HSF4 activates transcription of many genes required for proper lens development

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18
Q

Transcription factors

A

sequence specific DNA binding proteins which can directly or indirectly regulate transcription of genes

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19
Q

Transcription factor functional subregions

A

nuclear localization signal, DNA binding domain, TF interaction domains, most also contain protein interaction domains, some contain ligand binding domain, may contain transactivation or trans repression domains

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20
Q

protein interaction domains

A

allows transcription factors to recruit transcriptional regulatory protein complexes that can modify chromatin structure or activate or repress transcription

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21
Q

protein ligand binding domain

A

when occupied by ligand converts receptor to active transcription factor

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22
Q

transactivation and trans repression domains

A

can interact with and regulate activity of RNA polymerase II preinitation complex

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23
Q

Identified features HSF4

A

DNA binding domain, multifunctional domain (allows HSF4 to form trimers and interact with regulatory proteins), and transcriptionally activation domain

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24
Q

promotor

A

many DNA sequences that regulate transcription located here; consists of core promotor and proximal region; RNA pol II preinitiation complex binds to Tata box or equivalent DNA sequence just upstream of transcriptional start site

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25
Q

transcriptional regulatory DNA sequences

A

include response elements, enhancers, and silencers; regulatory sequences can also be found in distal sequences located upstream or down stream of TSS

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26
Q

Response elements

A

DNA sequences that transcription factors bind to, palindromic and non-palandromic

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27
Q

palindromic

A

reads same forwards one strand as other strand backwards; TFs (transcription factors) can bind to palindromic as homodimers or heterodimers

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28
Q

gene promotors and REs

A

gene promotors contain distance sets of REs but some genes may contain same REs so they can get cotranscribed

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29
Q

DNA of different cells in the body

A

cells in the body essentially contain all of the same DNA it is availability of transcription factors in a particular cell that dictates what genes get transcribed

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30
Q

Enhancers

A

TFs bind to REs in enhancer and interact and initiate transcription in a cell, tissue, or developmental specific manner

31
Q

why do enhancers function in a cell/ tissue/ stage of development ?

A

Because TF that binds and interacts at the enhancer only expressed and activated in specific cell or tissue or during a specific developmental stage

32
Q

enhancer location

A

can be upstream or downstream of core promotor and can act a a distance because distant regions of chromosomes can physically interact

33
Q

topologically associated domains

A

chromosomes can fold into spatially distinct chromatin compartments; contain looped DNA structures held together at their base by cohesion; may represent functionally distinct regions of genome that are independently regulated

34
Q

cohesion

A

multi-protein complex

35
Q

intrachromosomal looping

A

enables distant enhancer bound TFs and associated coregulators to interact with core promotors to facilitate the assembly and activation of RNA pol II preinitiation complex; looping helps control expression of tissue specific genes

36
Q

Enhancers and silencers relation to TAD

A

enhancers and silencers can only interact with and regulate genes in same TAD NOT those in adjacent TAD

37
Q

Gamma crystalliin

A

regulated by HSF4; stable interactions btwn crystalline proteins enable tight packed configuration; mutated HSF4 leads to reduction of gamma crystallin levels leading to destabilization of lens protein matrix leading to cataracts

38
Q

canine ectodermal dysplasia

A

autosomal semidominant leads to abnormalities in ectodermal appendages such as hair teeth nails sweat glands; Chinese crested hairless have this bc of a 7 basepair insertion resulting in FOXI3 protein being non functional

39
Q

FOXI3

A

this is non functional in canine ectodermal dysplasia; this encodes a transcription factor that is expressed in developing hair and teeth and is required for proper development of ectodermal appendages; this TF is in many tissues but is kept inactive

40
Q

Transcription factor activity or localiztion

A

signal’s from a cell’s internal and external environment regulate transcription of specific genes by controlling transcription factor activity or localization

41
Q

extracellular signals

A

hormones, growth factors, differentiation factors, ECM

42
Q

intracellular signals

A

DNA damage, organelle integrity, hypoxia, ROS, and pH

43
Q

signaling intermediates

A

many signaling intermediates are protein kinases that when activated can phosphorylate TF proteins or other proteins that can affect TF activity

44
Q

Transcription factors in the cytoplams

A

in the cytoplasm transcription factors are often sequestered by inhibitor proteins activated cell signaling kinases can promote release of or degradation of inhibitor so TF can go to nucleus and stimulate transcription

45
Q

mechanism of transcription for FOXI3 gene

A

ectodysplasin secreted by outer enamel ectodermal cells binds to its receptor EDAR on tooth precursor cells, activated receptor leads to signaling cascade, degradation inhibitor IkB, enabling TF NFkB to enter nucleus stimulating transcription of FOX13 gene

46
Q

Rdy

A

early onset rod-cone dysplasia in Abyssinians leads to aberrant photoreceptor development and degradation;bc of mutation to TF CDX (needed for photoreceptor cell development and survival); mutation leads to premature stop codon and CDX can’t stimulate transcription of target genes

47
Q

Chromatin role in controlling transcription

A

chromatin determines if TFs and RNA pol II pre initiation complex can access DNA; chromatin closed state is densely packed nucleosomes with pos histone tails interacting with histones of other nucleosomes, chromatin open state is transcriptionally active, characterized by decreased nucleosome density and packing

48
Q

regulating open and closed chromatin

A

done by protein complexes that regulate nucleosome positioning, density, and interactions;

49
Q

to activate transcription of a gene

A

HAT (histone acetyltransferase) and activating ATP-dependent chormatin remodeling proteins are recruited

50
Q

HAT

A

transfer acetyl group to basic amino acids neutralizing pos charge disrupting restrictive interactions between nucleosomes

51
Q

Activating ATP dependent chromatin remodeling proteins

A

alter nucleosome density and positioning either by promoting nucleosome disassembly or by altering the location of nucleosome relative to DNA; resulting chromatin is depleted of nucleosomes allowing access and transcription

52
Q

repress transcription of a gene

A

histone deacetyalase and repressing ATP dependent chromatin remodling protein restrict RNA pol II preinitiation complex and TF access to DNA

53
Q

histone deacetylase

A

removes acetyl groups from histone tail lysine restoring positive charges and in turn interactions between nucleosomes

54
Q

Repressing ATP dependent chromatin remodling protein

A

reestablish and maintain restrictive nucleosome density and positioning

55
Q

Chromatin modifieres

A

Chromatin modifying protein complexes recruited by TFs and by specific epigenetic modifications like DNA methylation and posttranslation histone tail modification; epigenetic modifications good bc reversible

56
Q

Histone modifictations writers

A

AA in N terminal tails of nucleosomal histones can be modified by methylation, phosphorylation, ubiquitination and acetylation; these are added by writer proteins

57
Q

histone modifications readers

A

histone modifications recognized by readers which can recruit additional proteins and protein complexes to regulate transcription

58
Q

histone modification erasers

A

remove specific histone modifications and allow new ones to be written

59
Q

regulatory complex

A

histone readers, writers, and erasers together; readers direct to specific histone modifications erasers and writers modify nearby histone marks

60
Q

Activating marks

A

associated with actively transcribed genes, enriched in chromatin of actively transcribed genes

61
Q

repressive marks

A

associated with repressed genes, enriched in chromatin of non-transcribed genes

62
Q

histone marks

A

can recruit proteins to modify chromatin structure to permit or inhibit transcription

63
Q

cancer and epigenetics

A

genes encoding histones and DNA modifiying enzymes are frequently mutated in many types cancer these enable epigenetic modifications that promote tumorigenesis (increasing transcription oncogenes decrasessig tumor suppressor genes)

64
Q

EZH2 misregulation

A

OVerexpression fo this gene or mutation lead to represses genes that would normally inhibit tumorigenesis

65
Q

Preinitiation complex

A

RNA Pol II part of this along with core promotor initiation factors (general TFs)

66
Q

RNA pol II

A

catalyzes RNA synth and contains c terminal tail which plays important role in regulation

67
Q

TFII-D

A

contains TATA binding protein which positions RNA PIC just upstream of transcriptional start site

68
Q

TFII-H

A

contains two enzymatic activities, helicase activity and protein kinase activty

69
Q

TFII-H helicase activity

A

unwinds DNA to expose template strand resulting in transcriptionally primed open complex

70
Q

TFII-H protein kinase activity

A

phosphorylates C terminal tail of Pol II

71
Q

mediator

A

large multisubunit protein complex communicates regulatory signals from TFs and coregulators to transcriptional machinery; recruited by enhancer bound TFs, brought close to core promotor via chromosomal looping, stimulates assembly and activation of RNA PIC

72
Q

RNA PIC assembly

A

after this template DNA is melted TFII-H helicase and polII initates transcription; TFII-H kinase phosphorylates c terminal tail enables transcription to continue and disentangles RNA pol II from RNA PIC (promotor escape)

73
Q

creation of functional mRNA

A

phosphorylated Pol II C-terminal tail recruited chromatin remodling elongation and RNA processing factors that are needed to process primary transcript and process it into functional mRNA

74
Q

RNA Pol II pausing

A

for many genes this pauses 30-60 nucleotides downstream of transcriptional start site; pausing mediated by inhibitory factors and by additional factors that stabilize its interaction with DNA; productive elongation restored after inactivation of pausing factors pausing allows for stable elongation complexes

Block Two Cell Bio (9 decks)

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