Walker Bridget M, Palumbo Ryan J, Knutson Bruce A
Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, New York, USA.
Dev Dyn. 2025 May 2. doi: 10.1002/dvdy.70029.
POLR1D is a shared subunit of RNA Polymerases I and III, which transcribe the rRNA incorporated into ribosomes. Mutations in POLR1D cause Treacher Collins syndrome, a craniofacial disorder that arises from impaired ribosome biogenesis in neural crest cells. Previously, we found that RNAi knockdown of Polr1D in several non-neural Drosophila tissues caused developmental defects that phenocopy mutations affecting ecdysone signaling. Ecdysone is a steroid hormone produced in the prothoracic gland (PG) of insects that triggers developmental transitions. Here, we show that Polr1D is required for PG development and ecdysone production to facilitate larval developmental transitions.
We found that Polr1D RNAi in the PG causes larval developmental arrest due to defective peripheral ecdysone signaling. We also found that Polr1D is required for the growth of PG cells and for maintaining nucleolar structure. We found that Polr1D is required for the synthesis of mature ribosomes and the production of the Pol III-transcribed 7SK RNA. Furthermore, developmental arrest of Polr1D RNAi larvae and Polr1D mutant (G30R) larvae was partially rescued by treatment with exogenous ecdysone.
These results demonstrate a role for Drosophila Polr1D in PG development and suggest that disruptions in human Polr1D might impact additional cell types during development.
POLR1D是RNA聚合酶I和III的共享亚基，负责转录并入核糖体的核糖体RNA。POLR1D突变会导致特雷彻·柯林斯综合征，这是一种颅面疾病，由神经嵴细胞中核糖体生物合成受损引起。此前，我们发现，在几种非神经果蝇组织中通过RNA干扰敲低Polr1D会导致发育缺陷，这些缺陷模拟了影响蜕皮激素信号传导的突变。蜕皮激素是昆虫前胸腺（PG）产生的一种类固醇激素，可触发发育转变。在此，我们表明，PG发育和蜕皮激素产生需要Polr1D来促进幼虫发育转变。
我们发现，PG中的Polr1D RNA干扰会导致幼虫发育停滞，原因是外周蜕皮激素信号传导缺陷。我们还发现，PG细胞生长和维持核仁结构需要Polr1D。我们发现，合成成熟核糖体和产生由Pol III转录的7SK RNA需要Polr1D。此外，用外源蜕皮激素处理可部分挽救Polr1D RNA干扰幼虫和Polr1D突变体（G30R）幼虫的发育停滞。
这些结果证明了果蝇Polr1D在PG发育中的作用，并表明人类Polr1D的破坏可能会在发育过程中影响其他细胞类型。
