Robust organismal development relies on temporal coordination of disparate physiological processes. In Caenorhabditis elegans, the heterochronic pathway controls a timely juvenile-to-adult (J/A) transition. This regulatory cascade of conserved proteins and small RNAs culminates in accumulation of the transcription factor LIN-29, which triggers coordinated execution of transition events. We report that two LIN-29 isoforms fulfill distinct functions. Functional specialization is a consequence of distinct isoform expression patterns, not protein sequence, and we propose that distinct LIN-29 dose sensitivities of the individual J/A transition events help to ensure their temporal ordering. We demonstrate that unique isoform expression patterns are generated by the activities of LIN-41 for lin-29a, and of HBL-1 for lin-29b, whereas the RNA-binding protein LIN-28 coordinates LIN-29 isoform activity, in part by regulating both hbl-1 and lin-41. Our findings reveal that coordinated transition from juvenile to adult involves branching of a linear pathway to achieve timely control of multiple events.

中文翻译：

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分支异时路径通过两个LIN-29亚型指导青少年到成人的过渡

健壮的有机体发育依赖于不同生理过程的时间协调。在秀丽隐杆线虫中，异时性途径控制着及时的青少年到成人（J / A）过渡。保守蛋白和小RNA的这种调节级联最终导致转录因子LIN-29的积累，从而触发了过渡事件的协调执行。我们报告说，两个LIN 29异构体履行不同的职能。功能专业化是不同的同工型表达模式而不是蛋白质序列的结果，并且我们提出单个J / A过渡事件的不同LIN-29剂量敏感性有助于确保其时间顺序。我们证明了独特的同工型表达模式是由LIN-41对lin-29a的活性产生的，和的HBL-1 LIN- 29 b，而RNA结合蛋白LIN-28坐标LIN-29同种型的活性，部分地通过调节两个HBL-1和LIN-41。我们的发现表明，从青少年到成年人的协调过渡涉及线性途径的分支，以实现对多个事件的及时控制。