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CONTROL OF GENE EXPRESSION IN EUKAR - Coggle Diagram
CONTROL OF GENE EXPRESSION IN EUKAR
Transcription factors - Transcriptional regulator proteins
điều hòa mức độ tương tác RNA polymerase và promoter
transcriptional activators and Coactivators
trực tiếp/ thông qua coactivators + DNA
activators: stimulate and stablizie the basal transcriptional apparatus
functions
khả năng liên kết với DNA tại vị trí đặc hiệu
usually in a regulatory promoter or enhancer (50-1500 Bp) - trước promotor vài genes
affects the assembly or stability of basal transcription apparatus
tương tác với các thành phần khác của basal transcription apparatus
bind to sequences and make contact with the mediator and affect the rate transcription (inititated)
mediator: One of the components of the
basal transcription apparatus is a complex of proteins
some of them, cùng với general transcription factors, have acetyltransferase activity -> altering chromatin structure, stimulate transcription
repressors
cạnh tranh trực tiếp
compete directly with transcriptonal activators - gắn vô regulator promoters
binds to site near an activator binding side -> prevent activator from contacting
possible mechanism
interference with assembly of basal transcription apparatus -> ngăn không cho khởi đầu PM
bind to regulator promoter or silencers (position and orientation independent = enhancers)
control through binding of proteins to DNA
transcriptional regulator proteins are required to bring normal levels of transcription
bind to a regulatory promoter (located upstream of the core promoter) and to enhancers
regulatory promoters: contain several different consensus sequences (conserved sequence motifs) -> activators can bind
activator binding sites are mixed and matched in different combinations -> each promoter is regulated by a unique COMBINATION of transcriptional activator proteins
enhancer affect the initiation of transcription at a promoter
transcriptional regulator proteins binds to enhancer -> hình hành cấu trúc vòng (loop)-> rút gắn vị trí enhancer và promotor -> regulator proteins tương tác với basal transcription apparatus
insulators
must lie between enhancer and promoter -> block the action of enhancer
maybe undergoing modifications -> alter chromatin structure
Transcriptional Stalling and Elongation
example
genes encode heat-shock proteins - help to prevent damage from heat stressor - in Drosophila - stalling khi được PM
khi có tín hiệu MT stress bởi nhiệt -> transcription of all heat-shock genes được đẩy mạnh
absense of stress, RNA polymerase stalls downstream ->released khi chống chọi với streass
stalling is widespread, occruring at 30%-50% of genes
one of factors promote stalling
negative elongation factor (NELF) - binds to RNA polymerase
positive transcription elongation factor b (P-TEFb). relieves stalling and promotes elongation by phosphoryling NELF and RNA polymerases
Coordinated gane regulation
several genes may be activated by the same stimulus
compared with bacteria: a cluster gene in an operon and share a promoter
HOW?
gennes share short regulatory sequences - RESPONSE ELEMENTS - in their promoters or enhancers
response elements
chứa nhiều trình tự bào tồn khác nhau ở các genes được điều khoa
binding sites for transcriptional activator proteins
a single gene may be regulated by several different response elements
1 response elements có thể elevate cho nhiều genes -> multiple genes are activated by different stimuli
summary
affect the initiation of transcription
change chromatin structure
transcription factors
transcriptional regulator
response elements
RNA processing
splicing
synthesis proteins depends on the amount of corresponding mRNA - availalbe for translation
rate of mRNA synthesis
rate of mRNA degradation
RNA processing and Degradation
RNA splicing
dependent on consesus sequences: 5'; 3' splice site and branch point
consesus sequences determine precise locations of introns and exons
exonic/intronic splicing enhencers/silencers - affect the use of particular splice sites -> alternative outcomes
proteins SR (serine and arginine rich)
influence the choice of splice sites is poorly understood
suggests: bind to enhancers > stimulate attachment of snRNPs -> commit the site to splicing
Degradation
thời gian tồn tại của mRNA ở Eukar là khác nhau -> ảnh hưởng lượng proteins đc synthesized
by ribonucleases, enzymes
pathways of degradations
5' cap first removed -> 5' - '3
Most common
when poly (A) tail has been shortened below a critical limit -> 5' cap is removed -> nucleases
explain: trong trước khi DM, mRNA sẽ tương tác với phức hệ protein khởi đầu PM trong đó eIF4E tương tác mũ 5'CAP, và eIF4G thì lại tương tác với PABPs -> mũ 5'Cap và đuôi polya A tương tác với nhau
3' end removes -> 3'-5' direction
mRNA is cleaved at internal sites
facilitated by small interfering RNA (siRNAs)
mRNAs containing AU-rich elements are degraded by microRNAs mechanism
does not required slicer activity like RNA interference
đóng góp trong precise regulation
sự trưởng thành của mRNA
gắn mũ 5' 7methylGuanine
bảo vệ pre-mRNA
đinh hướng mRNA đi chuyển ra ngoài nhân
gắn đuối poly(A)
giúp bảo vệ đầu 3' pre-mRNA
poly(A)-binding proteins (PABPs) bám vô
tăng tính bền của mRNA trước 3'-5' nuclease
tương tác với các nhân tố Phiên mã -> tạo thành cấu trúc vòng tái tạo liên tục của polysomes
RNA interference
known as RNA silencing or posstranscriptional gene silencing
30% of humnan genes are regulated by RNA interference
widely used as a technique for artificially regulating gene expression in genetically engineered
sản xuất siRNAs chức năng
siRNA: small interfering RNA
double stranded RNA -> cleaved by enz Dicer -> siRNAs -> combine with proteins to form RISC -> pair with mRNA and cleaves -> degraded
cleave mRNA gần khu vực lk của siRNA
microRNAs
double-stranded region (loop out) -> cleaved by Dicer -> microRNAs -> combine with protein to form RISC -> imperfectly pair with mRNA -> inhibition translation
functions: altering chromatin structures
siRNA liên kết bổ sung DNA and thu hút enzyme methylating enzymes -> methylate DNA or histones -> inhibit transcription (silencing)
siRNAs form RITS: RNA-induced transcriptional silencing
single stranded RNA sau khi được cắt: 21-25Nucletides
RISC: RNA-induced silencing complex
pair with mRNA, more often in 3'UTR
mechanism of regulation
cleavage of mRNA
contain an siRNA, cleave the mRNA near the middle of the bound siRNA
inhibition of translation
still poorly understood
transcriptional silencing
altering chromatin structure
binds to a complementary sequence in DNA - an RNA molecule in process of being transcribed
atracting enzymes methylate the tails of histone
degradation of RNA
does not require Slicer activity
contains an AU-rich element in 3' UTR
role in degradatuon of short-lived mRNAs
Modifications of proteins - process affect translation
eIF3
functions generally to initiate eukaryotic translation
either bind to secondary structures in 5' UTR - stimulate/repress
increasing overall of specific proteins, translational control can also target synthesis
the intiation is regulated by proteins that bind to 5'UTR -> inhibing the binding of ribosomes
affected by the binding to sequences 3' UTR