Cytoplasmic TAF2-TAF8-TAF10 complex provides evidence for nuclear holo-TFIID assembly from preformed submodules

General transcription factor TFIID is a cornerstone of RNA polymerase II transcription initiation in eukaryotic cells. How human TFIID-a megadalton-sized multiprotein complex composed of the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs)-assembles into a functional transcription factor is poorly understood. Here we describe a heterotrimeric TFIID subcomplex consisting of the TAF2, TAF8 and TAF10 proteins, which assembles in the cytoplasm. Using native mass spectrometry, we define the interactions between the TAFs and uncover a central role for TAF8 in nucleating the complex. X-ray crystallography reveals a non-canonical arrangement of the TAF8-TAF10 histone fold domains. TAF2 binds to multiple motifs within the TAF8 C-terminal region, and these interactions dictate TAF2 incorporation into a core-TFIID complex that exists in the nucleus. Our results provide evidence for a stepwise assembly pathway of nuclear holo-TFIID, regulated by nuclear import of preformed cytoplasmic submodules

Mapping and Functional Characterization of the TAF11 Interaction with TFIIA

TFIIA interacts with TFIID via association with TATA binding protein (TBP) and TBP-associated factor 11 (TAF11). We previously identified a mutation in the small subunit of TFIIA (toa2-I27K) that is defective for interaction with TAF11. To further explore the functional link between TFIIA and TAF11, the toa2-I27K allele was utilized in a genetic screen to isolate compensatory mutants in TAF11. Analysis of these compensatory mutants revealed that the interaction between TAF11 and TFIIA involves two distinct regions of TAF11: the highly conserved histone fold domain and the N-terminal region. Cells expressing a TAF11 allele defective for interaction with TFIIA exhibit conditional growth phenotypes and defects in transcription. Moreover, TAF11 imparts changes to both TFIIA-DNA and TBP-DNA contacts in the context of promoter DNA. These alterations appear to enhance the formation and stabilization of the TFIIA-TBP-DNA complex. Taken together, these studies provide essential information regarding the molecular organization of the TAF11-TFIIA interaction and define a mechanistic role for this association in the regulation of gene expression in vivo

African swine fever virus controls the host transcription and cellular machinery of protein synthesis

Throughout a viral infection, the infected cell reprograms the gene expression pattern in order to establish a satisfactory antiviral response. African swine fever virus (ASFV), like other complex DNA viruses, sets up a number of strategies to evade the host's defense systems, such as apoptosis, inflammation and immune responses. The capability of the virus to persist in its natural hosts and in domestic pigs, which recover from infection with less virulent isolates, suggests that the virus displays effective mechanisms to escape host defense systems. ASFV has been described to regulate the activation of several transcription factors, thus regulating the activation of specific target genes during ASFV infection. Whereas some reports have concerned about anti-apoptotic ASFV genes and the molecular mechanisms by which ASFV interferes with inducible gene transcription and immune evasion, less is yet known regarding how ASFV regulates the translational machinery in infected cells, although a recent report has shown a mechanism for favored expression of viral genes based on compartmentalization of viral mRNA and ribosomes with cellular translation factors within the virus factory. The viral mechanisms involved both in the regulation of host genes transcription and in the control of cellular protein synthesis are summarized in this review