A dual effect of FUBP1 on<i>SPA</i>lncRNA maturation

<i>SPA</i>s are noncanonical long noncoding RNAs (lncRNAs) that are 5' small nucleolar RNA (snoRNA) capped and 3' polyadenylated. Two <i>SPA</i>s are processed from a polycistronic transcript embedded in the human 15q11-q13 region related to Prader-Willi syndrome (PWS). Once produced, <i>SPA</i>s accumulate at their transcription site and sequester splicing factors to form PWS bodies that are involved in alternative splicing regulation. But how the processing of <i>SPA</i>s is regulated has remained obscure. Here, we identified that both far upstream element-binding protein 1 (FUBP1) and myelin expression factor 2 (MYEF2) were enriched in the PWS bodies; loss of either individually impaired <i>SPA</i>s' expression and dampened the size of PWS bodies in H9 and PA1 cells. Specifically, FUBP1, on the one hand, enhanced the transcription of <i>SPA</i>-embedded polycistronic transcripts by targeting the FUSE-like sequence upstream of the promoter, and on the other hand, was required for <i>SPA1</i> splicing and maturation by binding the uridine (U)-rich intronic sequences. These findings suggest a comprehensive and distinct regulation of PWS region-derived <i>SPA</i> lncRNAs.