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

Nepal, Chirag; Hadzhiev, Yavor; Balwierz, Piotr; Tarifeño-Saldivia, Estefanía; Cardenas, Ryan; Wragg, Joseph W; Suzuki, Ana-Maria; Carninci, Piero et al. · Nat Commun · 2020

basic_science · Level V

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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.

Medical subject headings