项目组多年来以长链非编码RNA(lncRNA)为研究特发性肺纤维化(IPF)发生机制的切入点，发现一条上调表达极显著的RNA转录本，命名为lncUTPF。体外翻译等实验证明其不具备编码能力，由其宿主基因Picalm的互补链转录而来，受到m6A甲基化修饰的影响。同时RNA-FISH等实验显示lncUTPF在胞核和胞质中均有分布，能与hnRNP A2B1/C1C2结合，形成RNA-蛋白复合物，调控端粒信号通路。. 该项目拟构建lncUTPF功能获得和缺失成纤维细胞和小鼠肺纤维化模型，研究lncUTPF的m6A甲基化修饰及在细胞质与细胞核中分别通过其宿主基因Picalm和hnRNP A2B1/C1C2-端粒信号通路调控肺纤维化发生的机制，揭示一个由非编码基因介导的遗传信息传递方式，为lncUTPF的临床应用和鉴定新的药物和基因治疗靶点提供思路和方案。

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic and progressive interstitial pneumonia of an unknown cause, and this disease leads to the progressive loss of lung function, respiratory failure, and death. To date, lung transplant is the only effective treatment available for IPF. Thus, a comprehensive understanding of the molecular mechanisms of fibrogenesis is required in developing specific therapies toward this disease.. The majority of genomes are transcribed using modern molecular biology techniques, such as deep sequencing; however, only 3% of the transcribed genome codes are attributed to proteins. The remaining part of the transcribed genome is known as noncoding RNA (ncRNA). ncRNAs can be divided into miRNA, long noncoding RNAs (lncRNA), ribosomal RNA and so on. Although lncRNA plays important roles in the development and progression of diseases, the mechanism of lncRNA in IPF remains unknown. This project is a follow-up to a previously completed research in our laboratory. In the present project, we defined a novel lncUTPF, its m6A methylation, and the crosstalk among its host gene Picalm and target protein hnRNP A2B1/C1C2-telomere signaling pathway in the regulation of fibrogenesis. . Over the years, our team has used long non-coding RNA (lncRNA) as the entry point for the study of the mechanism of IPF, and found an RNA transcript NONMMUT062668.2 with an extremely significant up-regulated expression. The transcript lacks the ability to encode a protein and is unreported lncRNA that is transcribed by the complementary strand of its host gene Picalm. M6A methylation effects its changes through methylation experiments. RNA pull down, mass spectrometry and other experimental results show that NONMMUT062668.2 can bind to hnRNP A2B1/C1C2 proteins to form RNA-protein complexes, bind to telomere single-stranded DNA, telomerase RNA, and holoenzymes to maintain telomerase activity and telomere length. So we named it lncUTPF (upregulated lncRNA associated with telomere in pulmonary fibrosis). . This project intends to use fibroblast model constructed by genome editing technology, mouse pulmonary fibrosis model and IPF patient specimen. What is the mechanism of lncUTPF m6A methylation and its regulatory host gene Picalm? How does it modulate the physiological and pathological states of telomeres by combining hnRNP A2B1/C1C2, leading to the occurrence of pulmonary fibrosis? Can it be used as a blood biomarker during the progress of pulmonary fibrosis? . All in all, our team try to reveal a genetic information transmission and regulatory network mediated by long non-coding genes, annotate and elucidate the structure and function of the genome from the perspective of protein coding genes, and provide candidate genes for IPF gene therapy or drug targets.