lincPeptEvolDev · LincRNA and encoded small peptides: Functional discovery in development and evolution

LincRNA and encoded small peptides: Functional discovery in development and evolution

Recent technological advances in DNA sequencing have led to a rapidly growing body of genomic information, wherein the genetic material from hundreds of plant and animal species, thousands of unique individuals, and many cancer types are now being catalogued. With this glut of genomic information, we are also making important discoveries about the complexity of our genomes, discovering new classes of functional elements that were previously unknown. These include functional RNA molecules from regions of the genome previously thought to be junk (including "long non-coding RNAs") and even new small protein units encoded in regions of coding and non-coding genes that were previously thought to be only regulatory. This project sought to identify novel functional protein molecules, called "micropeptides", a recently discovered class of tiny proteins that exist in all living things. We used a variety of insect model systems to identify potential functional micropeptides, by looking at their genomic sequences. We used evolutionary conservation as a beacon for candidates of interest, since evolutionary pressure causes a signature of protein sequence conservation, in a background where random mutation renders non-essential genome elements largely unrecognizable over time. Since insect development has been very well studied, and since genetic perturbations of these programs result in strong and distinctive defects, we focused on looking for conserved micropeptides that are expressed during development, and hoped that their mutation would lead to defects that would point us toward the part of development that is specifically affected. Identifying the functions of micropeptides is still one of the most challenging aspects of their study, since even by introducing mistakes into their sequence, it can be challenging to identify what consequence this has for a whole organism unless it is extremely significant. Still, this area of study is of great current interest, since small proteins like this class of naturally existing micropeptides, are able to integrate into a variety of cellular settings, and may represent a fruitful area of development for novel therapeutics that are able to affect a variety of cellular processes in a specific manner. Our overall objectives were to identify conserved insect micropeptides and to identify and study their functions, by introducing mutations that eliminate the function of these molecules, in order to identify the consequences of this loss of function. Our hope was that discovering and characterization of these tiny proteins would deepen our understanding of the functional capabilities of this class of molecules in general, and also specifically identify new functional elements that are critical components of developmental gene networks.

Data: CORDIS, © European Union