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The recognition of core promoter sequences by TFIID is the first step in RNA polymerase II (Pol II) transcription initiation. Metazoan holo-TFIID is a trilobular complex, composed of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs). Why and how TAFs are necessary for the formation of TFIID domains and how they contribute to transcription initiation remain unclear. Inducible TAF7 or TAF10 depletion, followed by comprehensive analysis of TFIID subcomplex formation, chromatin binding, and nascent transcription in mouse embryonic stem cells, result in the formation of a TAF7-lacking TFIID or a minimal core-TFIID complex, respectively. These partial complexes support TBP recruitment at promoters and nascent Pol II transcription at most genes early after depletion, but importantly, TAF10 is necessary for efficient Pol II pausing. We show that partially assembled TFIID complexes can sustain Pol II transcription initiation but cannot replace holo-TFIID over several cell divisions and/or development. [Display omitted] • TAF7 or TAF10 depletion leads to the formation of different partial TFIID complexes • Nascent Pol II transcription is not strongly affected in holo-TFIID-depleted cells • TBP is recruited at the promoter in holo-TFIID-depleted cells • Pol II pausing is affected in the absence of TAF10 Hisler et al. reveal that TAF7 and TAF10 depletion affects holo-TFIID sequential assembly, leading to the formation of partial TFIID complexes. Transcription is active and TBP is recruited at promoters when holo-TFIID is depleted. Partial TFIID complexes may sustain active transcription but cannot replace holo-TFIID over several cell divisions and/or development. [ABSTRACT FROM AUTHOR]

To understand the function of multisubunit complexes, it is of key importance to uncover the precise mechanisms that guide their assembly. Nascent proteins can find and bind their interaction partners during their translation, leading to co-translational assembly. Here, we demonstrate that the core modules of ATAC (ADA-two-A-containing) and SAGA (Spt-Ada-Gcn5-acetyltransferase), two lysine acetyl transferase-containing transcription co-activator complexes, assemble co-translationally in the cytoplasm of mammalian cells. In addition, a SAGA complex containing all of its modules forms in the cytoplasm and acetylates non-histone proteins. In contrast, ATAC complex subunits cannot be detected in the cytoplasm of mammalian cells. However, an endogenous ATAC complex containing two functional modules forms and functions in the nucleus. Thus, the two related co-activators, ATAC and SAGA, assemble using co-translational pathways, but their subcellular localization, cytoplasmic abundance, and functions are distinct. [Display omitted] • Core modules of ATAC and SAGA complexes assemble co-translationally in the cytoplasm • SAGA complex containing all of its subunits forms in the cytoplasm • SAGA complex acetylates non-histone proteins in the cytoplasm • ATAC complex can only be identified in the nucleus but not in the cytoplasm Yayli et al. find that modules of human ATAC (ADA-two-A-containing) and SAGA (Spt-Ada-Gcn5-acetyltransferase) transcriptional co-activator complexes assemble co-translationally in the cytoplasm. They describe that fully assembled SAGA has cytoplasmic acetylation functions. In contrast, the ATAC co-activator complex cannot be detected in the cytoplasm, only in the nucleus. [ABSTRACT FROM AUTHOR]

Completion of neuronal migration is critical for brain development. Kif21b is a plus-end-directed kinesin motor protein that promotes intracellular transport and controls microtubule dynamics in neurons. Here we report a physiological function of Kif21b during radial migration of projection neurons in the mouse developing cortex. In vivo analysis in mouse and live imaging on cultured slices demonstrate that Kif21b regulates the radial glia-guided locomotion of newborn neurons independently of its motility on microtubules. We show that Kif21b directly binds and regulates the actin cytoskeleton both in vitro and in vivo in migratory neurons. We establish that Kif21b-mediated regulation of actin cytoskeleton dynamics influences branching and nucleokinesis during neuronal locomotion. Altogether, our results reveal atypical roles of Kif21b on the actin cytoskeleton during migration of cortical projection neurons. [Display omitted] • Kif21b regulates neuronal migration independently of its motility on microtubules • Kif21b regulates actin cytoskeleton dynamics through direct binding • Kif21b function during nucleokinesis relies on the regulation of the actomyosin network • Kif21b fine-tunes actin dynamics during pausing and branching of migrating neurons Rivera Alvarez et al. show that the kinesin Kif21b regulates the migration of cortical neurons independently of its well-characterized motility function on microtubules. The authors demonstrate that Kif21b is an actin-binding protein that modulates both actin dynamics and actomyosin contraction in migrating neurons. [ABSTRACT FROM AUTHOR]