2026-03-03 理化学研究所,科学技術振興機構
マイクロペプチドタイマーによる細胞運命制御メカニズムの切り替え
＜関連情報＞
- https://www.riken.jp/press/2026/20260303_1/index.html
- https://www.pnas.org/doi/10.1073/pnas.2511138123
プリマイクロペプチドは細胞運命誘導の過渡期を制御する細胞内タイマーとして機能する Pri micropeptide functions as a cell-intrinsic timer controlling the transient phase of cell fate induction
Sonoko Mizuno, Tadashi Uemura, and Takefumi Kondo
Proceedings of the National Academy of Sciences Published:March 2, 2026
Significance
A large portion of the genome is transcribed into noncoding RNAs, some of which are actually translated into micropeptides from small open reading frames (sORFs). Numerous sORF-encoded micropeptides have been identified, but their functions have been demonstrated only in limited biological contexts, leaving it unclear how broadly they contribute to biological processes. Here, we show that the Drosophila micropeptide gene polished rice (pri) is key to inducing tracheal cell fate during embryogenesis. We further reveal that its transient expression acts as a molecular timer defining the time window for fate induction. This finding not only highlights the importance of sORF-encoded micropeptides in fate regulation but also proposes a mechanism for temporal control of cell fate decisions during development.
Abstract
During development, cells sequentially acquire specific fates through temporally ordered regulatory systems. To ensure the harmonious progression, each system must be activated and subsequently inactivated at the appropriate time. In this study, we show that the duration of fate induction is controlled by the transient expression of polished rice (pri), a gene encoding micropeptides, during Drosophila tracheal development. pri is transiently expressed in prospective tracheal placodes and precedes the expression of trachealess (trh), a master transcription factor that initiates tracheal fate. pri induces the expression of trh through promoting the disappearance of the repressor form of the transcriptional factor Shavenbaby (Svb). Conversely, after placode invagination, artificially prolonging pri expression or constitutive loss of Svb leads to ectopic maintenance of trh expression in noninvaginated placode cells surrounding the properly invaginated domain. These results indicate that the rapid disappearance of pri properly terminates the initial fate induction system and suggest that this termination ensures a smooth transition to the subsequent fate-regulatory program—that is, the maintenance of tracheal cell fate specifically in the invaginated cells. Together, we propose that the transiency of pri serves as a cell-intrinsic molecular timer that controls the transient phase of cell fate induction and ensures the transition between sequential fate-regulatory systems, thereby enabling the precise coordination of cell identity with morphogenesis during organogenesis.
