Transcription factor II A

Transcription factor TFIIA is a nuclear protein involved in the RNA polymerase II-dependent transcription of DNA.[1] TFIIA is one of several general (basal) transcription factors (GTFs) that are required for all transcription events that use RNA polymerase II. Other GTFs include TFIID, a complex composed of the TATA binding protein TBP and TBP-associated factors (TAFs), as well as the factors TFIIB, TFIIE, TFIIF, and TFIIH. Together, these factors are responsible for promoter recognition and the formation of a transcription preinitiation complex (PIC) capable of initiating RNA synthesis from a DNA template.

general transcription factor IIA, 1, 19/37kDa
Identifiers
SymbolGTF2A1
NCBI gene2957
HGNC4646
OMIM600520
RefSeqNM_201595
UniProtP52655
Other data
LocusChr. 14 q31
general transcription factor IIA, 2, 12kDa
Identifiers
SymbolGTF2A2
NCBI gene2958
HGNC4647
OMIM600519
RefSeqNM_004492
UniProtP52657
Other data
LocusChr. 15 q21.3

Functions

TFIIA interacts with the TBP subunit of TFIID and aids in the binding of TBP to TATA-box containing promoter DNA.[2][3] Interaction of TFIIA with TBP facilitates formation of and stabilizes the preinitiation complex. Interaction of TFIIA with TBP also results in the exclusion of negative (repressive) factors that might otherwise bind to TBP and interfere with PIC formation. TFIIA also acts as a coactivator for some transcriptional activators, assisting with their ability to increase, or activate, transcription. The requirement for TFIIA in vitro transcription systems has been variable, and it can be considered either as a GTF and/or a loosely associated TAF-like coactivator. Genetic analysis in yeast has shown that TFIIA is essential for viability.

Structure

TFIIA is a heterodimer with two subunits: one large unprocessed (subunit 1, or alpha/beta; gene name GTF2A1) and one small (subunit 2, or gamma; gene name GTF2A2).[4][5] It was originally believed to be a heterotrimer of an alpha (p35), a beta (p19) and a gamma subunit (p12). In humans, the sizes of the encoded proteins are approximately 55 kD and 12 kD. Both genes are present in species ranging from humans to yeast, and their protein products interact to form a complex composed of a beta barrel domain and an alpha helical bundle domain. It is the N-terminal and C-terminal regions of the large subunit that participate in interactions with the small subunit. These regions are separated by another domain whose sequence is always present in large subunits from various species but whose size varies and whose sequence is poorly conserved. A second gene encoding a large TFIIA subunit has been found in some higher eukaryotes. This gene, ALF/TFIIAtau (gene name GTF2A1LF) is expressed only in oocytes and spermatocytes, suggesting it has a TFIIA-like regulatory role for gene expression only in germ cells.

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References
  1. Høiby T, Zhou H, Mitsiou DJ, Stunnenberg HG (2007). "A facelift for the general transcription factor TFIIA". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1769 (7–8): 429–36. doi:10.1016/j.bbaexp.2007.04.008. PMID 17560669.
  2. Tang H, Sun X, Reinberg D, Ebright RH (February 1996). "Protein-protein interactions in eukaryotic transcription initiation: structure of the preinitiation complex". Proceedings of the National Academy of Sciences of the United States of America. 93 (3): 1119–24. doi:10.1073/pnas.93.3.1119. PMC 40041. PMID 8577725.
  3. Louder RK, He Y, López-Blanco JR, Fang J, Chacón P, Nogales E (March 2016). "Structure of promoter-bound TFIID and model of human pre-initiation complex assembly". Nature. 531 (7596): 604–9. doi:10.1038/nature17394. PMC 4856295. PMID 27007846.
  4. DeJong J, Roeder RG (November 1993). "A single cDNA, hTFIIA/alpha, encodes both the p35 and p19 subunits of human TFIIA". Genes & Development. 7 (11): 2220–34. doi:10.1101/gad.7.11.2220. PMID 8224848.
  5. Ozer J, Moore PA, Bolden AH, Lee A, Rosen CA, Lieberman PM (October 1994). "Molecular cloning of the small (gamma) subunit of human TFIIA reveals functions critical for activated transcription". Genes & Development. 8 (19): 2324–35. doi:10.1101/gad.8.19.2324. PMID 7958899.
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