Cross-species genome-wide identification of evolutionary conserved microProteins

Abstract

MicroProteins are small single-domain proteins that act by engaging their targets into different, sometimes nonproductive protein complexes. In order to identify novel microProteins in any sequenced genome of interest, we have developed miPFinder, a program that identifies and classifies potential microProteins. In the past years, several microProteins have been discovered in plants where they are mainly involved in the regulation of development by fine-tuning transcription factor activities. The miPFinder algorithm identifies all up to date known plant microProteins and extends the microProtein concept beyond transcription factors to other protein families. Here, we reveal potential microProtein candidates in several plant and animal reference genomes. A large number of these microProteins are species-specific while others evolved early and are evolutionary highly conserved. Most known microProtein genes originated from large ancestral genes by gene duplication, mutation and subsequent degradation. Gene ontology analysis shows that putative microProtein ancestors are often located in the nucleus, and involved in DNA binding and formation of protein complexes. Additionally, microProtein candidates act in plant transcriptional regulation, signal transduction and anatomical structure development. MiPFinder is freely available to find microProteins in any genome and will aid in the identification of novel microProteins in plants and animals.

Intriguing circles: Conflicts and controversies in circular RNA research

“…The protein encoded by circ‐SHPRH can act as a protective decoy molecule to decrease the degradation of its cognate full‐length protein, thus increasing the tumor suppressing role of this gene. Researchers also found an interesting phenomenon that some microproteins encoded by other RNA molecules can act like miRNAs and exert a negative function by heterodimerizing their target proteins into nonfunctional protein complexes (Eguen, Straub, Graeff, & Wenkel, ; Straub & Wenkel, ). However, to date, no circRNA has been reported to encode microproteins that act in this way.…”

Non-coding transcript variants of protein-coding genes – what are they good for?

“…Translatable exonic-circRNAs also very often generate polypeptides which resemble truncated versions of the proteins translated from their cognate mRNA pair [66]. Analogous to microRNAs, microproteins (miPs) are defined as small (< 120 residues), single domain polypeptides, which exert a dominant negative function by heterodimerizing their homologous target proteins into non-functional protein complexes [67,68]. Many of the non-coding splice-forms originally predicted to be NMD targets may be actively translated, providing miPs which interfere with the biological functions of the full length proteins encoded by their mRNA splice variants (Figure 2(d)).…”

Synthetic MicroProteins: Versatile Tools for Posttranslational Regulation of Target Proteins

“…MicroProtein candidates for Arabidopsis thaliana TAIR10 were taken from a published list 384 (Straub and Wenkel, 2017), and only conserved candidates were selected. The PANTHER 385 (Protein ANalysis THrough Evolutionary Relationships) (Mi et al, 2017) protein class (Mi et 386 al., 2013) of the putative ancestor with highest sequence similarity of the microProtein was 387 determined.…”