uORFdb—a comprehensive literature database on eukaryotic uORF biology

Abstract

Approximately half of all human transcripts contain at least one upstream translational initiation site that precedes the main coding sequence (CDS) and gives rise to an upstream open reading frame (uORF). We generated uORFdb, publicly available at http://cbdm.mdc-berlin.de/tools/uorfdb, to serve as a comprehensive literature database on eukaryotic uORF biology. Upstream ORFs affect downstream translation by interfering with the unrestrained progression of ribosomes across the transcript leader sequence. Although the first uORF-related translational activity was observed >30 years ago, and an increasing number of studies link defective uORF-mediated translational control to the development of human diseases, the features that determine uORF-mediated regulation of downstream translation are not well understood. The uORFdb was manually curated from all uORF-related literature listed at the PubMed database. It categorizes individual publications by a variety of denominators including taxon, gene and type of study. Furthermore, the database can be filtered for multiple structural and functional uORF-related properties to allow convenient and targeted access to the complex field of eukaryotic uORF biology.

Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames

“…In this context, the high number of translated uORFs within the core clock transcripts is particularly striking. uORF translation is generally viewed as inhibitory for protein production from the main ORF (Wethmar et al 2014) and represents an attractive mechanism for how clock protein levels (and consequently clock parameters) could be adjusted post-transcriptionally. It is tempting to speculate that one or several of the identified core clock uORFs are implicated in the short period phenotype observed in Denrdepleted cells.…”

“…These results are consistent with a prominent role for 5 ′ UTRs in translational control and with the idea that translation regulatory elements-of which longer 5 ′ UTRs potentially contain more-are predominantly inhibitory. Within 5 ′ UTRs, uORFs are emerging as important cis-regulatory elements that control CDS translation, usually in an inhibitory fashion (Wethmar et al 2014). Six percent of RPF-seq reads fell into annotated 5 ′ UTRs (Fig.…”

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

“…We first analyzed variants modifying upstream open reading frames (uORFs), which can alter protein expression by regulating translation (Wethmar et al 2014). In humans, approximately half of annotated transcripts contain uORFs, and presence of uORFs is widely polymorphic across individuals (Supplemental Table S5; Calvo et al 2009;Barbosa et al 2013;Waern and Snyder 2013).…”

The Plant Peptidome: An Expanding Repertoire of Structural Features and Biological Functions

“…For an overview of all plant uORFs, we refer to uORFdb, a database on eukaryotic uORF biology (http://cbdm. mdc-berlin.de/tools/uorfdb; Wethmar et al, 2014).…”