Abstract
Despite recent advances in developmental biology, and the sequencing and annotation of genomes, key questions regarding the organisation of cells into embryos remain. One possibility is that uncharacterised genes having nonstandard coding arrangements and functions could provide some of the answers. Here we present the characterisation of tarsal-less (tal), a new type of noncanonical gene that had been previously classified as a putative noncoding RNA. We show that tal controls gene expression and tissue folding in Drosophila, thus acting as a link between patterning and morphogenesis. tal function is mediated by several 33-nucleotide–long open reading frames (ORFs), which are translated into 11-amino-acid–long peptides. These are the shortest functional ORFs described to date, and therefore tal defines two novel paradigms in eukaryotic coding genes: the existence of short, unprocessed peptides with key biological functions, and their arrangement in polycistronic messengers. Our discovery of tal-related short ORFs in other species defines an ancient and noncanonical gene family in metazoans that represents a new class of eukaryotic genes. Our results open a new avenue for the annotation and functional analysis of genes and sequenced genomes, in which thousands of short ORFs are still uncharacterised.
Highlights
The work of the last decades has seen a breakthrough in our understanding of the genetic and molecular mechanisms of development
We expect that a combination of bioinformatic and functional methods, such as those presented in this study, will identify and characterise more genes of this type. These results suggest that hundreds of novel genes may await discovery
We expect that a combination of new bioinformatics and proteomics methods tailored to the search of peptides and small open reading frame (ORF) [19,20], plus a reassessment of classical data, will identify and characterise more new coding genes with important functions in these and other areas of biology
Summary
The work of the last decades has seen a breakthrough in our understanding of the genetic and molecular mechanisms of development. Classical genetic approaches have been complemented by systematic searches for new genes and their functions, resulting in an exponential increase of information. This new knowledge has filtered to related areas such as cell biology, medical research, and increasingly, evolution and population genetics. There still remain significant gaps in our understanding, of how different aspects of development such as patterning, morphogenesis, and differentiation are organised and implemented at the cellular level, and in how these different aspects are coordinated. The number of known key regulatory genes and signalling proteins remains small, in the region of the hundreds, but sequenced and annotated genomes, including the human genome, still contain thousands of genes and transcripts without known function or sequence similarity to other genes [1,2,3] or are deemed RNA or noncoding genes [4]
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