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

Abstract

Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase IItranscribed 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.

Is the Secret of VDAC Isoforms in Their Gene Regulation? Characterization of Human VDAC Genes Expression Profile, Promoter Activity, and Transcriptional Regulators

“…In P VDAC2 ( Figure 5 a) and P VDAC3 ( Figure 5 c) a non-canonical initiation site termed the TCT motif (polypyrimidine initiator) was identified. The polypyrimidine stretch proximal to the 5′ end of these genes was a target for translation regulation, oxidative and metabolic stress, or cancer-induced differential translational regulation by the mTOR pathway [ 37 ].…”

Embryonic tissue differentiation is characterized by transitions in cell cycle dynamic-associated core promoter regulation

“…Nano-CAGE reads were trimmed (15 bp from 5′end) to remove the linker and unique molecular identifier (UMI) region. For previously published data reanalysed in this study, raw CAGE sequencing data was downloaded from the repositories detailed in the respective publications ( 17 , 30 , 31 ). Reads were mapped using Bowtie ( 32 ), allowing a maximum of two mismatches and only uniquely mapping tags with MAPQ of 20.…”

Human library of cardiac promoters and enhancers

“…To compare the two groups (promoters and enhancers), we selected two subsets of data. To represent the promoters, we have chosen those TSS that were annotated as "true," then we have selected the start site with the highest CAGE expression as the "best" TSS per gene (10,206 TSS).…”

“…Deep sequencing of CAGE libraries allows precise estimation of expression at the promoter level for coding and noncoding transcripts. This approach is useful for alternative promoter identification, which might affect final protein structure, or even estimate short TSS shifts linked to regulatory network features 10,11 . Such cis-regulatory elements interact with enhancers and result in cell-typespecific expression profiles, while understanding of underlying molecular mechanisms and the network itself remains incomplete.…”