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J. Cardiovasc. Dev. Dis. 2018, 5(2), 26; https://doi.org/10.3390/jcdd5020026

The Role of scaRNAs in Adjusting Alternative mRNA Splicing in Heart Development

1
College of Biosciences, Kansas City University, Kansas City, MO 64106, USA
2
Ward Family Heart Center, Children’s Mercy Hospital, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA
3
Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan
These two authors contributed equally to this manuscript.
*
Author to whom correspondence should be addressed.
Received: 30 March 2018 / Revised: 27 April 2018 / Accepted: 3 May 2018 / Published: 8 May 2018
(This article belongs to the Special Issue Genetics of Congenital Heart Disease)
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Abstract

Congenital heart disease (CHD) is a leading cause of death in children <1 year of age. Despite intense effort in the last 10 years, most CHDs (~70%) still have an unknown etiology. Conotruncal based defects, such as Tetralogy of Fallot (TOF), a common complex of devastating heart defects, typically requires surgical intervention in the first year of life. We reported that the noncoding transcriptome in myocardial tissue from children with TOF is characterized by significant variation in levels of expression of noncoding RNAs, and more specifically, a significant reduction in 12 small cajal body-associated RNAs (scaRNAs) in the right ventricle. scaRNAs are essential for the biochemical modification and maturation of small nuclear RNAs (spliceosomal RNAs), which in turn are critical components of the spliceosome. This is particularly important because we also documented that splicing of mRNAs that are critical for heart development was dysregulated in the heart tissue of infants with TOF. Furthermore, we went on to show, using the zebrafish model, that altering the expression of these same scaRNAs led to faulty mRNA processing and heart defects in the developing embryo. This review will examine how scaRNAs may influence spliceosome fidelity in exon retention during heart development and thus contribute to regulation of heart development. View Full-Text
Keywords: alternative mRNA splicing; congenital heart defects; scaRNAs; small cajal body-associated RNAs; tetralogy of Fallot alternative mRNA splicing; congenital heart defects; scaRNAs; small cajal body-associated RNAs; tetralogy of Fallot
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Nagasawa, C.; Ogren, A.; Kibiryeva, N.; Marshall, J.; O’Brien, J.E.; Kenmochi, N.; Bittel, D.C. The Role of scaRNAs in Adjusting Alternative mRNA Splicing in Heart Development. J. Cardiovasc. Dev. Dis. 2018, 5, 26.

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