As conserved components of the transcription factor (TF) IID-and TFTC/SAGA-related complexes, TATAbinding protein-associated factors (TAF II s) are important for eukaryotic mRNA transcription. In yeast, genetic analyses suggest that, although some individual TAF II s are required for transcription of most genes, others have highly specialized functions. Much less is known about the functions of TAF II s in metazoans, which have more complex genomes that include many tissue-specific genes. TAF-5 (human (h) TAF II 100) is of particular interest because it is predicted to have an important structural role. Here we describe the first genetics-based analysis of TAF-5 in a metazoan. By performing RNA interference in Caenorhabditis elegans embryos, which can survive for several cell generations without transcription, we found that taf-5 is important for a significant fraction of transcription. However, TAF-5 is apparently not essential for the expression of multiple developmental and other metazoan-specific genes. This phenotype remarkably resembles the previously described effects of similarly depleting two C. elegans histone fold TAF II s, TAF-9 (hTAF II 31/32) and TAF-10 (hTAF II 30), but is distinct from the widespread transcription block caused by TAF-4 (hTAF II 130) depletion. Our findings suggest that TAF-5, TAF-9, and TAF-10 are part of a functional module of TFIID-and TFTC/ SAGA-related complexes that can be bypassed in many metazoan-specific genes.Eukaryotic mRNA transcription requires the coordinate activity of gene-specific activators, coactivator proteins, general transcription factors (TFIIA, 1 TFIIB, TFIID, TFIIE, TFIIF, and TFIIH), Mediator complexes, and RNA polymerase II (pol II) (1-3). This complexity allows the transcription machinery to communicate with gene-specific regulators through an extraordinary diversity of combinatorial interactions. Genetic studies performed in yeast indicate that, although many transcription machinery components are essential, others seem to perform more specialized roles in regulating subgroups of genes (4 -6). In general, genes involved in maintenance of cell viability are shared by all eukaryotes, suggesting that aspects of their regulation are likely to be conserved between yeast and metazoans. However, most metazoan genes, including those controlling development and differentiation, are not conserved in single cell eukaryotes and may require alternative regulatory strategies (7,8).The general transcription factor TFIID is composed of the TATA-binding protein along with 12-14 additional polypeptides, the TATA-binding protein-associated factors (TAF II s) 2 (5, 9, 10). The TAF II s are generally conserved in eukaryotes (11). TFIID has various functions during initiation; it appears to possess enzymatic activities, and TAF II s have been implicated in essential interactions with gene-specific activators and with core promoter sequences located near the transcription start site (5, 9, 12, 13). Many TAF II s contain a domain that is related to the histone fold, through w...