New insights into minor splicing—a transcriptomic analysis of cells derived from TALS patients

• DOI: 10.1261/rna.071423.119
• Publication Date: 2019-06-07T19:15:15Z
• Authors: Audric Cologne; Clara Benoit-Pilven; Alicia Besson; Audrey Putoux; Amandine Campan-F...; Michael B. Bober; Christine E.M. De...; Aimee D.C. Paulussen; Lucile Pinson; Annick Toutain; Chaim M. Roifman; Anne-Louise Leute...; Sylvie Mazoyer; Patrick Edery; Vincent Lacroix
• Keywords: Spliceosome; Splice site mutation; Small nuclear RNA; Precursor mRNA

Minor intron splicing plays a central role in human embryonic development and survival. Indeed, biallelic mutations RNU4ATAC , transcribed into the minor spliceosomal U4atac snRNA, are responsible for three rare autosomal recessive multimalformation disorders named Taybi–Linder (TALS/MOPD1), Roifman (RFMN), Lowry–Wood (LWS) syndromes, which associate numerous overlapping signs of varying severity. Although RNA-seq experiments have been conducted on few RFMN patient cells, none performed TALS, more generally no in-depth transcriptomic analysis ∼700 genes containing (U12-type) had published as yet. We thus sequenced RNA from cells derived five skin, amniotic fluid, one blood biosamples obtained seven unrelated TALS cases age- sex-matched controls. This allowed us to describe first time mRNA expression profile U12-type introns, context functional spliceosome. Concerning -mutated patients, we show that expected, they display distinct profiles compared controls, but rather unexpectedly levels mostly unchanged. Furthermore, although missplicing concerns most expressed U12 genes, level retention is surprisingly low fibroblasts amniocytes, much pronounced cells. Interestingly, found several occurrences introns can be spliced using either U2, U12, or combination both types splice site consensus sequences, with shift towards preferentially U2 sites patients’