Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing
Chirag Nepal, Yavor Hadzhiev, Piotr J. Balwierz, Estefanía Tarifeño-Saldivia, Ryan Cardenas, Joseph W. Wragg, Ana-Maria Suzuki, Piero Carninci, Bernard Peers, Boris Lenhard, Jesper B. Andersen, Ferenc Müller
Abstract
Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry polypyrimidine initiator (5'-TOP or TCT). By addressing the developmental regulation of TSS selection in zebrafish we uncovered a class of dual-initiation promoters in thousands of genes, including snoRNA host genes. 5'-TOP/TCT initiation is intertwined with canonical initiation and used divergently in hundreds of dual-initiation promoters during maternal to zygotic transition. Dual-initiation in snoRNA host genes selectively generates host and snoRNA with often different spatio-temporal expression. Dual-initiation promoters are pervasive in human and fruit fly, reflecting evolutionary conservation. We propose that dual-initiation on shared promoters represents a composite promoter architecture, which can function both coordinately and divergently to diversify RNAs.