Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing

Chirag Nepal (), Yavor Hadzhiev, Piotr Balwierz, Estefanía Tarifeño-Saldivia, Ryan Cardenas, Joseph W. Wragg, Ana-Maria Suzuki, Piero Carninci, Bernard Peers, Boris Lenhard, Jesper B. Andersen and Ferenc Müller ()
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Chirag Nepal: University of Copenhagen
Yavor Hadzhiev: University of Birmingham
Piotr Balwierz: University of Birmingham
Estefanía Tarifeño-Saldivia: Université de Liège
Ryan Cardenas: University of Birmingham
Joseph W. Wragg: University of Birmingham
Ana-Maria Suzuki: RIKEN Center for Life Science Technologies
Piero Carninci: RIKEN Center for Life Science Technologies
Bernard Peers: Université de Liège
Boris Lenhard: Imperial College London
Jesper B. Andersen: University of Copenhagen
Ferenc Müller: University of Birmingham

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-019-13687-0

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