Transcript Eukaryotic Transcription

Eukaryotic Transcription
Eukaryotic Transcriptional
• Transcription control is the most important mode
of control in eukaryotes.
• Three RNA polymerases:
– RNA Polymerase I: synthesis of pre-rRNA, which is
processed into 28S, 5.8S, and 18S rRNAs
– RNA polymerase III: synthesis of tRNA, 18 S rRNA,
and small, stable RNAs
– RNA polymerase II: synthesis of mRNAs and four
small nuclear RNAs that take part in RNA splicing
Eukaryotic Transcriptional
• The main purpose is the execution of
precise developmental decisions
(irreversible).
• Cis-acting control elements are located
many kb away from the start site.
• Promoter region is poorly characterized.
TATA box
About 25-35 bp upstream of the start site
5’
+1
TATAAA
-34 to
-26
mRNA start
Well-defined
transcription start
Initiator
• Instead of a TATA box, some eukaryotic
gene contain an alternative promoter
element, called an initiator.
• Initiator is highly degenerative.
+1
5’ Y Y A N T/A Y Y Y
Y = pyrimidine (C or T)
N = any
CpG island
• Genes coding for intermediary metabolism are
transcribed at low rates, and do not contain a TATA box
or initiator.
• Most genes of this type contain a CG-rich stretch of 2050 nt within ~100 bp upstream of the start site region.
• A transcription factor called SP1 recognizes these CGrich region.
• Gives multiple alternative mRNA start sites.
~100 bp
CpG island
mRNA
Multiple
5’-start sites
Enhancers
• Located several Kb away from the start
site.
• Usually ~100-200 bp long, containing
multiple 8- to 20-bp control elements.
• Cell-type specific
• Direction-less (invertible)
+1
Enhancer
Enhancer
Promoter Proximal Elements
•
•
•
•
Occur within ~200 bp of the start site.
Contain up to ~20 bp.
Cell-type specific
Invertible
+1
Promoter
Proximal
element
A hypothetic mammalian promoter
region
Promoter
Proximal
Element
+1
Enhancer
Enhancer
-10~-50 Kb
-200
TATA
-30
Intron
Exon
Enhancer
+10~50 Kb
A hypothetic yeast promoter region
+1
Enhancer
TATA
~-90
mRNA processing
Poly (A) site
Exon
Cap
Intron
Termination
transcription
5’
The 5’-Cap is added to Nascent RNAs (pre-RNAs) shortly after initiation
by RNA polymerase II.
Pre-mRNAs are associated with hnRNP (heterogeneous
ribonucleoprotein particles) proteins containing conserved
RNA-binding domains
Poly (A) site
Exon
Intron
Termination
Cap
5’
Cap
endonuclease
5’
5’
Poly(A) polymerase
A100-250
Pre-mRNAs are cleaved at specific 3’ sites and rapidly polyadenylated
Cleavage and polyadenylation
Poly(A) signal Poly(A) site
5’
AAUAAA
G/U rich
Pre-mRNA
5’
AAUAAA
AAAAAA100-250
Poly (A) site
Exon
Intron
Termination
Cap
5’
endonuclease
5’
Poly(A) polymerase
A100-250
5’
RNA splicing
5’
A100-250