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bioRxiv · 10.1101/2025.06.23.660276

Cotranslational assembly confers specificity for in vivo target heterodimerization of paralogous H2B-like TAF12 proteins in the human fungal pathogen Candida albicans

Bhardwaj, V.·Swanson, S.·Florens, L.·Washburn, M. P.·Workman, J. L.·Natarajan, K.
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Abstract

The fidelity of assembly of multiprotein complexes is essential for the formation of stable and functional protein complexes that are critical for cell growth and survival. In this context, TBP-associated factor (TAF) subunits maintain tight specificity for their integration into TFIID and SAGA complexes. In this work, using affinity purification-coupled mass spectrometry of epitope-tagged TFIID subunits TBP and TAF11, and the SAGA subunit TAF12L we identified components of the C. albicans TFIID and SAGA complexes. Whereas TAF12 is a subunit of TFIID, the paralogous TAF12L is a subunit of the SAGA complex, and we further identified each of the TFIID and SAGA complex subunits with high confidence. We found that the steady-state levels of the H2B-H2A-like histone fold domain containing pairs, TAF12-TAF4 and TAF12L-Ada1 proteins, are mutually dependent on the stable expression of each other. Using RNA coimmunoprecipitation from polysome-containing extracts, we found that nascent TAF4 and Ada1 proteins interact with TAF12 and TAF12L, respectively, by a cotranslational mechanism in an ordered, sequential mode of assembly. Thus, our results indicate that heterodimerization of the TAF12 paralogs with cognate partners occur by sequential cotranslational assembly thereby ensuring both selectivity and stability of the H2A-H2B heterodimers in fungal pathogen C. albicans.

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Bhardwaj, V., Swanson, S., Florens, L., Washburn, M. P., Workman, J. L., Natarajan, K.. 2025-06-26. Cotranslational assembly confers specificity for in vivo target heterodimerization of paralogous H2B-like TAF12 proteins in the human fungal pathogen Candida albicans. https://doi.org/10.1101/2025.06.23.660276

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