A dual-effect of FUBP1 on the SPA lncRNA maturation.

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.