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Recent findings have revealed that many genomic regions previously annotated as non-protein coding actually contain small open reading frames, smaller that 300 bp, that are transcribed and translated into evolutionary conserved microproteins. To date, only a small subset of them have been functionally characterized, but they play key functions in fundamental processes such as DNA repair, RNA processing and metabolism regulation. This emergent field seems to hide a new category of molecular regulators with clinical potential. In this review, we focus on its relevance for cancer. Following Hanahan and Weinberg's classification of the hallmarks of cancer, we provide an overview of those microproteins known to be implicated in cancer or those that, based on their function, are likely to play a role in cancer. The resulting picture is that while we are at the very early times of this field, it holds the promise to provide crucial information to understand cancer biology. [ABSTRACT FROM AUTHOR]

High throughput RNA sequencing techniques have revealed that a large fraction of the genome is transcribed into long non-coding RNAs (lncRNAs). Unlike canonical protein-coding genes, lncRNAs do not contain long open reading frames (ORFs) and tend to be poorly conserved across species. However, many of them contain small ORFs (sORFs) that exhibit translation signatures according to ribosome profiling or proteomics data. These sORFs are a source of putative novel proteins; some of them may confer a selective advantage and be maintained over time, a process known as de novo gene birth. Here we review the mechanisms by which randomly occurring sORFs in lncRNAs can become new functional proteins. [ABSTRACT FROM AUTHOR]

Recent ribosome profiling and proteomic studies have revealed the presence of thousands of novel coding sequences, referred to as small open reading frames (sORFs), in prokaryotic and eukaryotic genomes. These genes have defied discovery via traditional genomic tools not only because they tend to be shorter than standard gene annotation length cutoffs, but also because they are, as a class, enriched in sequence properties previously assumed to be unusual, including non-AUG start codons. In this review, we summarize what is currently known about the incidence, efficiency, and mechanism of non-AUG start codon usage in prokaryotes and eukaryotes, and provide examples of regulatory and functional sORFs that initiate at non-AUG codons. While only a handful of non-AUG-initiated novel genes have been characterized in detail to date, their participation in important biological processes suggests that an improved understanding of this class of genes is needed. [ABSTRACT FROM AUTHOR]

Growing evidence illustrates the shortcomings on the current understanding of the full complexity of the proteome. Previously overlooked small open reading frames (sORFs) and their encoded microproteins have filled important gaps, exerting their function as biologically relevant regulators. The characterization of the full small proteome has potential applications in many fields. Continuous development of techniques and tools led to an improved sORF discovery, where these can originate from bioinformatics analyses, from sequencing routines or proteomics approaches. In this mini review, we discuss the ongoing trends in the three fields and suggest some strategies for further characterization of high potential candidates. [ABSTRACT FROM AUTHOR]

Proteins are critical components of biological membranes and play key roles in many essential cellular processes. Membrane proteins are a structurally and functionally diverse family of proteins that have recently expanded to include a number of newly discovered tiny proteins called microproteins, or micropeptides. These microproteins are generated from small open reading frames, which produce protein products that are less than 100 amino acids in length. While not all microproteins are membrane proteins, this review will focus specifically on this subclass to highlight some of the important biological activities that have been ascribed to these molecules and to emphasize their promise as exciting new players in membrane biology. [ABSTRACT FROM AUTHOR]