Snord94 expression level alters methylation at C62 in snRNA U6


Autoři: Allison Ogren aff001;  Nataliya Kibiryeva aff002;  Jennifer Marshall aff002;  James E. O’Brien, Jr. aff002;  Douglas C. Bittel aff001
Působiště autorů: College of Biosciences, Kansas City University of Medicine and Biosciences (KCU), Kansas City, MO, United States of America aff001;  Ward Family Heart Center, Children’s Mercy Hospital, Kansas City, MO, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226035

Souhrn

Understanding the regulation of development can help elucidate the pathogenesis behind many developmental defects found in humans and other vertebrates. Evidence has shown that alternative splicing of messenger RNA (mRNA) plays a role in developmental regulation, but our knowledge of the underlying mechanisms that regulate alternative splicing are incomplete. Notably, a subset of small noncoding RNAs known as scaRNAs (small cajal body associated RNAs) contribute to spliceosome maturation and function through guiding covalent modification of spliceosomal RNAs with either methylation or pseudouridylation on specific nucleotides, but the developmental significance of these modifications is not well understood. Our focus is on one such scaRNA, known as SNORD94 or U94, that guides methylation on one specific cytosine (C62) on spliceosomal RNA U6, thus potentially altering spliceosome function during embryogenesis. We previously showed that in the myocardium of infants with heart defects, mRNA is alternatively spliced as compared to control tissues. We also demonstrated that alternatively spliced genes were concentrated in the pathways that control heart development. Furthermore, we showed that modifying expression of scaRNAs alters mRNA splicing in human cells, and zebrafish embryos. Here we present evidence that SNORD94 levels directly influence levels of methylation at its target region in U6, suggesting a potential mechanism for modifying alternative splicing of mRNA. The potential importance of scaRNAs as a developmentally important regulatory mechanism controlling alternative splicing of mRNA is unappreciated and needs more research.

Klíčová slova:

Alternative splicing – Methylation – Polymerase chain reaction – Small nuclear RNA – Small nucleolar RNA – Spliceosomes – Heart development


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Článek vyšel v časopise

PLOS One


2019 Číslo 12