Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The yeast HIS3 TR and TC TATA elements support basal transcription, but only TR can respond to transcriptional activators. Four genes, NOT1(CDC39), NOT2(CDC36), NOT3, NOT4, act as general negative regulators and preferentially affect TC-dependent transcription. Allele-specific suppression, a two-hybrid interaction, and biochemical confractionation suggest that NOT1 and NOT2 are nuclear proteins associated in a discrete, 500-kD complex. NOT4 interacts with NOT1 and NOT3 in the two-hybrid assay, and overexpression of NOT3 or NOT4 suppresses not1 and not2 mutations. Repression by the NOT proteins is not attributable to inhibition of transcriptional activators, does not involve the CYC8/TUP1 negative regulatory complex, and is distinct from repression by nucleosomes or by the SPT4, 5, 6 proteins that affect chromatin structure. We propose that the NOT protein inhibit the basic RNA polymerase II transcription machinery, possibly by affecting TFIID function.
 ...
PMID:NOT1(CDC39), NOT2(CDC36), NOT3, and NOT4 encode a global-negative regulator of transcription that differentially affects TATA-element utilization. 792 48

The CCR4-NOT complex (1 mDa in size), consisting of the proteins CCR4, CAF1, and NOT1 to NOT5, regulates gene expression both positively and negatively and is distinct from other large transcriptional complexes in Saccharomyces cerevisiae such as SNF/SWI, TFIID, SAGA, and RNA polymerase II holoenzyme. The physical and genetic interactions between the components of the CCR4-NOT complex were investigated in order to gain insight into how this complex affects the expression of diverse genes and processes. The CAF1 protein was found to be absolutely required for CCR4 association with the NOT proteins, and CCR4 and CAF1, in turn, physically interacted with NOT1 through its central amino acid region from positions 667 to 1152. The NOT3, NOT4, and NOT5 proteins had no significant effect on the association of CCR4, CAF1, and NOT1 with each other. In contrast, the NOT2, NOT4, and NOT5 interacted with the C-terminal region (residues 1490 to 2108) of NOT1 in which NOT2 and NOT5 physically associated in the absence of CAF1, NOT3, and NOT4. These and other data indicate that the physical ordering of these proteins in the complex is CCR4-CAF1-NOT1-(NOT2, NOT5), with NOT4 and NOT3 more peripheral to NOT2 and NOT5. The physical separation of CCR4 and CAF1 from other components of the CCR4-NOT complex correlated with genetic analysis indicating partially separate functions for these two groups of proteins. ccr4 or caf1 deletion suppressed the increased 3-aminotriazole resistance phenotype conferred by not mutations, resulted in opposite effects on gene expression as compared to several not mutations, and resulted in a number of synthetic phenotypes in combination with not mutations. These results define the CCR4-NOT complex as consisting of at least two physically and functionally separated groups of proteins.
 ...
PMID:The CCR4 and CAF1 proteins of the CCR4-NOT complex are physically and functionally separated from NOT2, NOT4, and NOT5. 1049 Jun 3

The yeast CCR4-NOT protein complex is a global regulator of RNA polymerase II transcription. It is comprised of yeast NOT1 to NOT5, yeast CCR4 and additional proteins like yeast CAF1. Here we report the isolation of cDNAs encoding human NOT2, NOT3, NOT4 and a CAF1-like factor, CALIF. Analysis of their mRNA levels in different human tissues reveals a common ubiquitous expression pattern. A multitude of two-hybrid interactions among the human cDNAs suggest that their encoded proteins also form a complex in mammalian cells. Functional conservation of these proteins throughout evolution is supported by the observation that the isolated human NOT3 and NOT4 cDNAs can partially com-plement corresponding not mutations in yeast. Interestingly, human CALIF is highly homologous to, although clearly different from, a recently described human CAF1 protein. Conserved interactions of this factor with both NOT and CCR4 proteins and co-immunoprecipitation experiments suggest that CALIF is a bona fide component of the human CCR4-NOT complex.
 ...
PMID:Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits. 1063 34

The CCR4-NOT transcriptional regulatory complex affects transcription both positively and negatively and consists of the following two complexes: a core 1 x 10(6) dalton (1 MDa) complex consisting of CCR4, CAF1, and the five NOT proteins and a larger, less defined 1.9-MDa complex. We report here the identification of two new factors that associate with the CCR4-NOT proteins as follows: CAF4, a WD40-containing protein, and CAF16, a putative ABC ATPase. Whereas neither CAF4 nor CAF16 was part of the core CCR4-NOT complex, both CAF16 and CAF4 appeared to be present in the 1.9-MDa complex. CAF4 also displayed physical interactions with multiple CCR4-NOT components and with DBF2, a likely component of the 1.9-MDa complex. In addition, both CAF4 and CAF16 were found to interact in a CCR4-dependent manner with SRB9, a component of the SRB complex that is part of the yeast RNA polymerase II holoenzyme. The three related SRB proteins, SRB9, SRB10, and SRB11, were found to interact with and to coimmunoprecipitate DBF2, CAF4, CCR4, NOT2, and NOT1. Defects in SRB9 and SRB10 also affected processes at the ADH2 locus known to be controlled by components of the CCR4-NOT complex; an srb9 mutation was shown to reduce ADH2 derepression and either an srb9 or srb10 allele suppressed spt10-enhanced expression of ADH2. In addition, srb9 and srb10 alleles increased ADR1(c)-dependent ADH2 expression; not4 and not5 deletions are the only other known defects that elicit this phenotype. These results suggest a close physical and functional association between components of the CCR4-NOT complexes and the SRB9, -10, and -11 components of the holoenzyme.
 ...
PMID:Characterization of CAF4 and CAF16 reveals a functional connection between the CCR4-NOT complex and a subset of SRB proteins of the RNA polymerase II holoenzyme. 1111 36

In African trypanosomes, there is no control of transcription initiation by RNA polymerase II at the level of individual protein-coding genes. Transcription is polycistronic, and individual mRNAs are excised by trans-splicing and polyadenylation. As a consequence, trypanosomes are uniquely reliant on post-transcriptional mechanisms for control of gene expression. Rates of mRNA decay vary over up to two orders of magnitude, making these organisms an excellent model system for the study of mRNA degradation processes. The trypanosome CAF1-NOT complex is simpler than that of other organisms, with no CCR4 or NOT4 homolog: it consists of CAF1, NOT1, NOT2, NOT5 NOT9, NOT10, and NOT11. It is important for the initiation of degradation of most, although not all, mRNAs. There is no homolog of NOT4, and Tho and TREX complexes are absent. Functions of the trypanosome NOT complex are therefore likely to be restricted mainly to deadenylation. Mechanisms that cause the NOT complex to deadenylate some mRNAs faster than others must exist, but have not yet been described.
...
PMID:The CAF1-NOT complex of trypanosomes. 2442 69