Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
Nat Struct Mol Biol. 2024 Nov;31(11):1650-1654. doi: 10.1038/s41594-024-01361-z. Epub 2024 Jul 18.
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 长非编码 RNA 协调副核体组装并影响肿瘤发生、生育和免疫。其成熟需要 RNase P 切割，由于 CCACCA 的添加，产生不稳定的转移 RNA 样多发性内分泌肿瘤-β 样 tRNA 转录本 (menRNA)。在这里，我们报告了人 menRNA 的晶体结构，该结构部分模拟 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、类似核糖体开关的机制，其中新生的 CCA 重塑 RNA 折叠景观，并推动自发的构象异构化，从而指导重复 CCA 的添加，标记 menRNA 和有缺陷的 tRNA 进行降解。
