Gene expression is regulated at both transcriptional and posttranscriptional levels. Posttranscriptional control mechanisms include altered mRNA stability, and/or regulation of mRNA translation. In general, mRNA is composed of translated coding sequence (CDS) and untranslated regions (UTRs). The 5’ untranslated region (5’ UTR), as an important mediator of translational regulation, contains many different elements, such as internal ribosome entry sites (IRESs), G-quadruplexes, and Kozak consensus sequences. Upstream open reading frames (uORFs) are typically defined as coding sequences located upstream of the main coding sequence (CDS) initiation site within 5’ UTR. Besides, considerable uORFs are overlapping with main codon regions. It is reported that uORFs are fairly common occurring in nearly half of all human genes. In addition, there are abundant mRNA modifications in 5’ UTR, such as N6-Methyladenosine (m6A), N1-methyladenosine (m1A), and N7-methylguanosine (m7G), among which m6A have been revealed to play important roles in translation regulation by dynamic regulating uORF functionalities. However, a comprehensive resource for uORFs is currently lacking. Considering a large amount of ribosome profiling (Ribo-seq) data and a considerable amount of quantitative translation initiation sequencing (QTI-seq) data for human and mouse in GEO database, a comprehensive uORF database, based on the extensive amount of available Ribo-seq data, and offering user-friendly analysis tools, is urgently needed to help characterize uORF-mediated gene expression.
Here, we developed Ribo-uORF to serve as a comprehensive functional resource for uORF analysis based on ribosome profiling (Ribo-seq) data. Ribo-uORF currently supports six species including human, mouse, rat, zebrafish, fly, and worm. Ribo-uORF includes 501,554 actively translated uORFs and 107,914 upstream translation initiation sites (uTIS), identified from 1,495 Ribo-seq and 77 quantitative translation initiation sequencing (QTI-seq) datasets, respectively. Moreover, mRNAbrowser was developed to visualize uORFs, cis-regulatory elements, genetic variations, eQTLs, GWAS, RNA modifications, and RNA editing, etc. Ribo-uORF provides a very intuitive web interface for users to intuitively and conveniently browse, search, and visualize data. Meanwhile, uORFscan and UTR5var were developed in Ribo-uORF to precisely identify uORFs and annotate the influence of genetic mutations on uORFs using user-uploaded datasets. Taken together, Ribo-uORF will likely greatly facilitate studies of uORFs and roles in mRNA translation initiation and the posttranscriptional control of gene expression.

Ribo-uORF: a comprehensive data resource of upstream open reading frames (uORFs) based on ribosome profiling

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