Taf11-KO Mouse

Taf11, also known as TATA-binding protein-associated factor 11, is involved in multiple biological processes. It is an annotated nuclear transcription factor and is part of the general transcription factor TFIID complex, which is crucial for RNA polymerase II transcription initiation [3,4]. Taf11 also has a role in cytoplasmic functions related to RNA-induced silencing complex (RISC) assembly, enhancing RNAi efficiency [1].

Genetic screen in Drosophila identified Taf11 as the missing factor of the RISC loading complex (RLC). Taf11 associates with Dcr-2/R2D2 and localizes to cytoplasmic D2 bodies. In taf11(-/-) ovary extract, RLC assembly is defective, and in vitro reconstitution of RLC using recombinant Dcr-2-R2D2 complex, Taf11, and duplex siRNA demonstrated that Taf11 tetramer facilitates Dcr-2-R2D2 tetramerization to enhance siRNA binding and RISC loading activities [1]. In a Chinese pedigree, a Taf11 variant (NC_000006.12: g.34887814C>G) was identified in non-syndromic cleft lip only (NSCLO) cases. The mutant G allele increased Taf11 expression, which downregulated CDH1 and CTNND1 in the cell adhesion pathway by binding to their promoter regions. Overexpression of Taf11 in zebrafish led to disturbed migration of cranial neural crest cells and abnormal craniofacial development [2].

In conclusion, Taf11 has diverse functions. Its role in RLC assembly and enhancement of RNAi efficiency in Drosophila reveals its importance in post-transcriptional gene regulation. In the context of human disease, its variant is associated with NSCLO through modulation of cell adhesion-related genes and neural crest cell migration, providing insights into the molecular mechanisms underlying this craniofacial disorder.

References:

1. Liang, Chunyang, Wang, Yibing, Murota, Yukiko, Siomi, Mikiko C, Liu, Qinghua. 2015. TAF11 Assembles the RISC Loading Complex to Enhance RNAi Efficiency. In Molecular cell, 59, 807-18. doi:10.1016/j.molcel.2015.07.006. https://pubmed.ncbi.nlm.nih.gov/26257286/

2. Li, Dandan, Tian, Yu, Vona, Barbara, Wang, Lin, Pan, Yongchu. . A TAF11 variant contributes to non-syndromic cleft lip only through modulating neural crest cell migration. In Human molecular genetics, 34, 392-401. doi:10.1093/hmg/ddae188. https://pubmed.ncbi.nlm.nih.gov/39727181/

3. Robinson, M M, Yatherajam, G, Ranallo, R T, Paule, M R, Stargell, L A. . Mapping and functional characterization of the TAF11 interaction with TFIIA. In Molecular and cellular biology, 25, 945-57. doi:. https://pubmed.ncbi.nlm.nih.gov/15657423/

4. Gupta, Kapil, Watson, Aleksandra A, Baptista, Tiago, Tora, Làszlò, Berger, Imre. 2017. Architecture of TAF11/TAF13/TBP complex suggests novel regulation properties of general transcription factor TFIID. In eLife, 6, . doi:10.7554/eLife.30395. https://pubmed.ncbi.nlm.nih.gov/29111974/