Evolution from an intronic Alu insertion generates a human-specific TAF8 isoform contributing to TFIID assembly complexity in the human lineage

ABSTRACT: Despite its centrality in the regulation of RNA polymerase II transcription in all eukaryotes, the general transcription factor TFIID exhibits several layers of variability in different tissues and developmental stages, representing an underexplored hub of evolutionary innovations. Here we describe the existence of a novel short isoform of TAF8 (TAF8s) – a scaffold TFIID subunit – which evolved from the usage of an intronic polyadenylation site (iPAS) in the human lineage. Comparative genomics analyses show that the emergence of TAF8s expression in the human lineage coincides with minute DNA changes in the iPAS at the edge of a FLAM-C Alu element that inserted into intron 5 in the common ancestor of anthropoid primates (Simiiformes). The human-specific TAF8s isoform lacks nearly half of the canonical CDS, is widely expressed across human tissues, and constitutes a substantial fraction of the TAF8 transcript pool. TAF8s is translated into a truncated protein isoform that lacks the nuclear-localization signal and localises in the cytoplasm. TAF8s interacts with its histone-fold partner TAF10 and other core TFIID subunits, while entirely losing its interactions with TAF2, thus giving rise to alternative TFIID sub-complexes in human cells. Our study suggests that the TFIID complex underwent a recent diversification through a stepwise evolutionary acquisition of complexity in the TAF8 locus in the human lineage, leading to the expression of a novel truncated pan-isoform that might work as a modulator of TFIID assembly. We discuss the ramifications of our findings in TFIID complex diversification, its evolvability, and the genetics of TAF-related congenital disorders.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Bastien Morlet  

LAB HEAD: Dr Andrea Bernardini

PROVIDER: PXD072860 | Pride | 2026-10-28

REPOSITORIES: Pride