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Nat Commun. 2020 Jan 10;11(1):168. doi: 10.1038/s41467-019-13687-0.

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

Author information

1
Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Ole Maaloes Vej 5, 2200, Copenhagen, Denmark. chirag.nepal@bric.ku.dk.
2
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
3
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, W12 0NN, London, UK.
4
MRC Clinical Sciences Centre, Hammersmith Hospital Campus, W12 0NN, London, UK.
5
Laboratory for Molecular Biology and Genetic Engineering, GIGA-R, Université de Liège, Liège, Belgium.
6
Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile.
7
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
8
Laboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
9
Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Ole Maaloes Vej 5, 2200, Copenhagen, Denmark.
10
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. f.mueller@bham.ac.uk.

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.

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