Proteins regulating eukaryotic mRNA synthesis

1

• Proteins regulating eukaryotic mRNA
  synthesis
• General transcription factors
• TFIID (a multisubunit protein) binds to the TATA
  box
• to begin the assembly of the transcription
  apparatus
• the TATA binding protein (TBP) directly binds
  the TATA box
• TBP associated factors (TAFs) bind to TBP
• TFIIA, TFIIB, TFIIE, TFIIF, TFIIH1, TFIIJ
  assemble with TFIID
• RNA polymerase II binds the promoter region via
  the TFIIs
• Transcription factors binding to other promoter
  elements and
• transcription elements interact with
  proteins at the promoter
• and further stabilize (or inhibit)
  formation of a functional
• preinitiation complex
• 1TFIIH is also involved in phosphorylation of RNA
  polymerase II, DNA repair
• (Cockayne syndrome mutations), and cell cycle
  regulation

2
Binding of the general transcription factors
F
TAFs
E
TFIID
B
H
TBP
A
J
1
-25

• TFIID (a multisubunit protein) binds to the TATA
  box
• to begin the assembly of the transcription
  apparatus
• the TATA binding protein (TBP) directly binds
  the TATA box
• TBP associated factors (TAFs) bind to TBP
• TFIIA, TFIIB, TFIIE, TFIIF, TFIIH, TFIIJ
  assemble with TFIID

3
Binding of RNA polymerase II
F
E
TFIID
B
H
TBP
A
J
RNA pol II

• RNA polymerase II (a multisubunit protein) binds
  to
• the promoter region by interacting with the
  TFIIs
• TFs recruit histone acetylase to the promoter

4
Binding of specialized TFs
F
E
TFIID
B
H
TBP
A
J
1
RNA pol II

• transcription factors binding to
• other promoter elements and transcription
  elements interact
• with proteins at the promoter and further
  stabilize (or inhibit)
• formation of a functional preinitiation
  complex
• this process is called transactivation

5
Binding of AP1 to DNA transactivates transcription
F
P
E
Jun
Fos
TFIID
B
H
TBP
A
J
1
RNA pol II

• Binding of AP1 to its
• DNA transcription element (TGACTCA)
  stimulates
• RNA synthesis by interacting with the
  preinitiation complex
• Activity of AP1 can be further regulated by
  phosphorylation
• by Jun N-terminal kinase (JNK junk kinase)

6
Formation of a stable preinitiation complex
F
E
B
TFIID
H
TBP
J
1
RNA pol II

• the stability and frequency with which complexes
  are formed
• determines the rate of initation of
  transcription
• the rate of initiation of transcription is of
  major importance in
• determining the abundance of an mRNA
  species

7
Initiation of transcription and promoter clearance
Entire Complex70 polypeptides,3MDa (ribosome)
F
E
B
TFIID
H
initiation
TBP
J
1
RNA pol II
CTD
P
P
P

• RNA pol II is phosphorylated by TFIIH on the
  carboxy terminal
• domain (CTD), releasing it from the
  preinitiation complex and
• allowing it to initiate RNA synthesis and move
  down the gene