Small peptide regulators of actin-based cell morphogenesis encoded by a polycistronic mRNA

Abstract

Transcriptome analyses in eukaryotes, including mice and humans, have identified polyA-containing transcripts that lack long open reading frames (ORFs; >100 amino acids). These transcripts are believed most likely to function as non-coding RNAs, but their translational capacities and biological activities have not been characterized in detail. Here, we report that polished rice (pri), which was previously identified as a gene for a non-coding RNA in Drosophila, is in fact transcribed into a polycistronic mRNA that contains evolutionarily conserved short ORFs that encode 11 or 32 amino acid-long peptides. pri was expressed in all epithelial tissues during embryogenesis. The loss of pri function completely eliminated apical cuticular structures, including the epidermal denticles and tracheal taenidia, and also caused defective tracheal-tube expansion. We found that pri is essential for the formation of specific F-actin bundles that prefigures the formation of the denticles and taenidium. We provide evidences that pri acts non-cell autonomously and that four of the conserved pri ORFs are functionally redundant. These results demonstrate that pri has essential roles in epithelial morphogenesis by regulating F-actin organization.

Hidden Peptides Encoded by Putative Noncoding RNAs

“…ORFs 1 to 3 encode peptides of 11 amino acids, whereas ORF 4 encodes a peptide of 32 amino acids. The phenotype of pri-deficient mutant flies was completely rescued by introduction of ORFs 1 to 4 individually, suggesting that the encoded common amino acid sequence is responsible for pri function (Kondo et al, 2007).…”

Long Noncoding RNAs: Past, Present, and Future

“…However, an interesting twist in the ncRNA debate occurred when a developmentally important Drosophila transcript previously thought to be noncoding, called tarsal-less or polished rice, was found to be a polycistronic mRNA that encodes multiple short (11-32 amino acids) but functional peptides, and this gene structure is conserved among insects (Galindo et al 2007;Kondo et al 2007Kondo et al , 2010. More recently, ribosome-profiling experiments in mouse ES cells revealed that the majority of lncRNAs are in fact translated into small peptides (Ingolia et al 2011).…”

Tracheal branching morphogenesis inDrosophila: new insights into cell behaviour and organ architecture

“…A novel type of tracheal tube expansion gene is polished rice (pri; also known as tarsal-less), which is transcribed into a polycistronic mRNA that encodes multiple evolutionarily conserved open reading frames of 11 or 32 amino acids (Kondo et al, 2007). pri functions non-cell autonomously, indicating that these small peptides might travel through extracellular space to coordinate ECM organization.…”

“…It is thought that one of these putative chitin deacetylases, encoded by a gene called vermiform (verm; LCBP1 -FlyBase), is delivered to the apical lumen via a specialized secretory pathway that requires septate junctions; this is suggested by the observation that Verm is not properly secreted into the luminal space in several mutants of septate junction components, whereas Pio, for example, is normally secreted into the apical luminal space in the same mutants (Luschnig et al, 2006;Wang et al, 2006). The lack of Verm secretion in many septate junction mutants could indeed account for the tube-lengthexpansion defects that are observed in the absence of several septate junction components (such as Claudin, Megatrachea, Neurexin IV, Gliotactin and Neuroglian) (reviewed in Swanson and Beitel, 2006), but the exact role of septate junction components in secretion remains to be investigated.A novel type of tracheal tube expansion gene is polished rice (pri; also known as tarsal-less), which is transcribed into a polycistronic mRNA that encodes multiple evolutionarily conserved open reading frames of 11 or 32 amino acids (Kondo et al, 2007). pri functions non-cell autonomously, indicating that these small peptides might travel through extracellular space to coordinate ECM organization.…”