Methylation at nucleotide C⁶² in spliceosomal RNA U6 alters mRNA splicing which is important for embryonic development

Abstract

DCB) 9 3 31under investigation. Alternative splicing of mRNA transcripts of genes is tissue and time specific 32 throughout life, although this process occurs everywhere in the body according to local tissue 33 needs and signals. The spliceosome, the large ribonucleoprotein complex that carries out splicing, 34 is biochemically modified by small noncoding RNAs, which is important for its structure and 35 function. Here we show that the amount of 2'-O-ribose methylation at nucleotide C 62 in 36 spliceosomal RNA U6 is dependent on the level of the scaRNA SNORD94. We hypothesize that 37 alternative splicing is dependent, at least in part, on biochemical modification to the spliceosomal 38 RNAs. Furthermore, when scaRNA directed modifications are dysregulated, the result causes 39 inappropriate alternative splicing that may contribute to developmental defects such as 40 congenital heart defects. To our knowledge, this is the first demonstration that 2'-O-ribose 41 methylation is indeed dependent on scaRNA levels in human cells and tissues. 42

Small but strong: the emerging role of small nucleolar RNA in cardiovascular diseases

“…These observations strongly suggest that snoRNAs and snRNAs are necessary for normal cardiac development. Furthermore, Ogren et al reported that methylation in the target region of SNORD94 on U6 is decreased in right ventricular myocardium tissue of infants with TOF compared with that of the control (Ogren et al, 2019). Additionally, cell culture experiments revealed that, by changing the levels of SNORD94, a corresponding change in methylation at C 62 within the snRNA U6 is produced.…”