Eukaryotic Transcription II

Which factors are required for global transcription?

Genome-wide expression analysis was used to identify genes whose expression depends on the functions of key components of the transcription initiation machinery in yeast (Figure N4). The mRNA levels of 5460 genes were accurately determined using high-density olionucleotide arrays.

Transcriptional Machinery (Cell 95, 717-728, 1998)
 Complex and Subunit  Features

Percent of dependent genes
 RNA pol II: Rpb1 Largest subunit

100
 SRB/MED: Srb4 Target of Gal4 activator

100
 SRB/MED: Med6

10
 SRB/MED: Srb10 CTD kinase, negative reg.

3
 SWI/SNF: Swi2 ATP-dependent chromatin remodeling

6
 SAGA: TAF17 Component of SAGA and TFIID

67
  SAGA: Gcn5 Histone acetylase

 5
GTF: TFIID (TAFII 145) Histone acetylase

16
GTF: TFIIH (Kin28) CTD kinase

87

Fidelity in RNA polymerase II transcription

From: Thomas et al. (1998) Cell 93, 627-637. Factor SII (or TFIIS) stimulates an intinsic RNA cleavage activity of RNA polymerase II. In the presence of SII, pol II quantitatively removes misincorporated nucleotides from the nascent transcript during rapid chain elongation. The basis of discrimination between the correct and incorrect base is the slow addition of the next nucleotide to the mismatched terminus. SII can also rescue arrested complexes and allow the resumption of elongation. Thus, TFIIS plays a role similar to the E. coli GreA and GreB factors.

Capping

Modification of the 5'-ends of eukaryotic mRNAs is called capping. The cap consists of a methylated GTP linked to the rest of the mRNA by a 5' to 5' triphosphate "bridge"(Cap Structure). Capping occurs very early during the synthesis of eukaryotic mRNAs, even before mRNA molecules are finished being made by RNA polymerase II. Capped mRNAs are very efficiently translated by ribosomes to make proteins. In fact, some viruses, such as poliovirus, prevent capped cellular mRNAs from being translated into proteins. This enables poliovirus to take over the protein synthesizing machinery in the infected cell to make new viruses.

Polyadenylation

Modification of the 3'-ends of eukaryotic mRNAs is called polyadenylation (Polyadenylation Pathway). Polyadenylation is the addition of several hundred A nucleotides to the 3' ends of mRNAs. All eukaryotic mRNAs destined to get a poly A tail (note: most, but not all, eukaryotic mRNAs get such a tail) contain the sequence AAUAAA about 11-30 nucleotides upstream to where the tail is added. AAUAAA is recognized by an endonuclease that cuts the RNA, allowing the tail to be added by a specific enzyme: polyA polymerase.

Regulation of Polyadenylation