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.
Highlights
Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates
We demonstrate the pervasive nature of noncanonical YC transcription initiation, intertwined with canonical YR-initiation, within the core promoter of thousands of genes in three model species
TCT initiation has been shown to be activated by a distinct set of core promoter binding transcription factors, highlighting its distinct function[39] regulation by TBP family member TRF213 and distinct enhancer interaction specificity[14]
Summary
Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Sequencing of capped RNA 5′ ends by CAGE (cap-analysis of gene expression) revealed that an overwhelming majority of TSSs are anchored by a purine base at the start site (+1 position) and flanked by pyrimidine in the upstream region (−1 position), defining consensus Y−1R+1 (hereafter called YR-initiation) as canonical initiator in mammals[2] and in teleosts (zebrafish and tetraodon)[3], suggesting generality of conserved initiator among vertebrates. Transcription initiation of translation-associated genes (ribosomal proteins, snoRNA host genes, translation initiation, and elongation factors) is anchored by C+1 (cytosine) and flanked by a polypyrimidine stretch[6,7,8,9,10,11] These non-canonical initiators have previously been termed 5′-TOP (terminal oligo-polypyrimidine) in mammalian systems or TCT initiators in Drosophila[12] Initiation in the same core promoter region, revealing thousands of what we term dual-initiation (DI) promoter genes
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