上海科技大学知识管理系统

SPAs are noncanonical long noncoding RNAs (lncRNAs) that are 5' small nucleolar RNA (snoRNA) capped and 3' polyadenylated. Two SPAs are processed from a polycistronic transcript embedded in the human 15q11-13 region related to Prader-Willi Syndrome (PWS). Once produced, SPAs accumulate at their transcription site and sequester splicing factors to form PWS-related nuclear bodies that are involved in alternative splicing regulation. But how the processing of SPAs is regulated has remained obscure. Here, we identified both Far upstream element-binding protein 1 (FUBP1) and Myelin expression factor 2 (MYEF2) enriched in the PWS-related nuclear bodies, loss of both, individually, impaired SPAs expression and dampened the size of PWS-related nuclear bodies in H9 and PA1 cells. Specifically, FUBP1 on the one hand enhances SPAs transcription by targeting the FUSE-like sequence upstream of the polycistronic transcript promoter, and on the other hand, is required for SPA1 splicing and maturation by binding the uridine (U)-rich intronic sequences. These findings suggest a comprehensive and distinct regulation of PWS region-derived SPA lncRNAs.