Work

A dual effect of FUBP1 onSPAlncRNA maturation

Year: 2025

Type: article

Abstract: SPAs are noncanonical long noncoding RNAs (lncRNAs) that are 5′ small nucleolar RNA (snoRNA) capped and 3′ polyadenylated. TwoSPAs are processed from a polycistronic transcript embedded in the human 15q11-q13 region related to Prader–Willi syndrome (PWS). Once produced,SPAs accumulate at their transcription site and sequester splicing factors to form PWS bodies that are involved in alternative splicing regulation. But how the processing ofSPAs 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 impairedSPAs’ expression and dampened the size of PWS bodies in H9 and PA1 cells. Specifically, FUBP1, on the one hand, enhanced the transcription ofSPA-embedded polycistronic transcripts by targeting the FUSE-like sequence upstream of the promoter, and on the other hand, was required forSPA1splicing and maturation by binding the uridine (U)-rich intronic sequences. These findings suggest a comprehensive and distinct regulation of PWS region-derivedSPAlncRNAs.

Source: RNA

DOI: 10.1261/rna.080341.124