NEAT1 long noncoding RNA orchestrates paraspeckle assembly and impacts tumorigenesis, fertility and immunity. Its maturation requires RNase P cleavage yielding an unstable transfer RNA-like multiple endocrine neoplasia-β tRNA-like transcript (menRNA) due to CCACCA addition. Here we report the crystal structure of human menRNA, which partially mimics tRNAs to drive RNase P and ELAC2 processing. Biophysical analyses uncover an RNA-centric, riboswitch-like mechanism whereby the nascent CCA reshapes the RNA folding landscape and propels a spontaneous conformational isomerization that directs repeat CCA addition, marking the menRNA and defective tRNAs for degradation.

NEAT1 长链非编码 RNA 协调副斑组装并影响肿瘤发生、生育能力和免疫力。由于 CCACCA 的添加，它的成熟需要 RNase P 切割产生不稳定的转移 RNA 样多发性内分泌腺瘤β tRNA 样转录物 （menRNA）。在这里，我们报道了人 menRNA 的晶体结构，它部分模拟 tRNA 以驱动 RNase P 和 ELAC2 加工。生物物理分析揭示了一种以 RNA 为中心的核糖开关样机制，其中新生的 CCA 重塑了 RNA 折叠景观并推动了自发的构象异构化，从而指导重复的 CCA 添加，标记 menRNA 和缺陷的 tRNA 进行降解。