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:
https://doi.org/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
Zdroje
1. National Heart B, and Lung Institute. Congenital Heart Defects. Available from: https://www.nhlbi.nih.gov/health-topics/congenital-heart-defects.
2. Gelb BD, Chung WK. Complex genetics and the etiology of human congenital heart disease. Cold Spring Harbor perspectives in medicine. 2014;4(7):a013953. Epub 2014/07/06. doi: 10.1101/cshperspect.a013953 24985128; PubMed Central PMCID: PMC4066638.
3. O'Brien JE Jr., Kibiryeva N, Zhou XG, Marshall JA, Lofland GK, Artman M, et al. Noncoding RNA expression in myocardium from infants with tetralogy of Fallot. Circulation Cardiovascular genetics. 2012;5(3):279–86. Epub 2012/04/25. doi: 10.1161/CIRCGENETICS.111.961474 22528145.
4. Hartman JL, Garvik B, Hartwell L. Principles for the Buffering of Genetic Variation. Science. 2001;291(5506):1001–4. doi: 10.1126/science.291.5506.1001 11232561
5. Rutherford SL, Henikoff S. Quantitative epigenetics. Nature Genetics. 2003;33:6–8. doi: 10.1038/ng0103-6 12509772
6. Nagasawa C, Ogren A, Kibiryeva N, Marshall J, O’Brien J, Kenmochi N, et al. The Role of scaRNAs in Adjusting Alternative mRNA Splicing in Heart Development. Journal of Cardiovascular Development and Disease. 2018;5(2):26. doi: 10.3390/jcdd5020026 29738469
7. Wessels MW, Willems PJ. Genetic factors in non-syndromic congenital heart malformations. Clinical genetics. 2010;78(2):103–23. Epub 2010/05/26. doi: 10.1111/j.1399-0004.2010.01435.x 20497191.
8. Patil P, Kibiryeva N, Uechi T, Marshall J, O'Brien JE Jr., Artman M, et al. scaRNAs regulate splicing and vertebrate heart development. Biochimica et biophysica acta. 2015;1852(8):1619–29. Epub 2015/04/29. doi: 10.1016/j.bbadis.2015.04.016 25916634.
9. Will CL, Luhrmann R. Spliceosome structure and function. Cold Spring Harbor perspectives in biology. 2011;3(7). Epub 2011/03/29. doi: 10.1101/cshperspect.a003707 21441581; PubMed Central PMCID: PMC3119917.
10. Bland CS, Wang ET, Vu A, David MP, Castle JC, Johnson JM, et al. Global regulation of alternative splicing during myogenic differentiation. Nucleic Acids Research. 2010;38(21):7651–64. doi: 10.1093/nar/gkq614 PMC2995044. 20634200
11. Kalsotra A, Cooper TA. Functional consequences of developmentally regulated alternative splicing. Nature reviews Genetics. 2011;12(10):715–29. Epub 2011/09/17. doi: 10.1038/nrg3052 21921927; PubMed Central PMCID: PMC3321218.
12. Kalsotra A, Wang K, Li PF, Cooper TA. MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development. Genes & development. 2010;24(7):653–8. Epub 2010/03/20. doi: 10.1101/gad.1894310 20299448; PubMed Central PMCID: PMC2849122.
13. Salomonis N, Nelson B, Vranizan K, Pico AR, Hanspers K, Kuchinsky A, et al. Alternative splicing in the differentiation of human embryonic stem cells into cardiac precursors. PLoS computational biology. 2009;5(11):e1000553. Epub 2009/11/07. doi: 10.1371/journal.pcbi.1000553 19893621; PubMed Central PMCID: PMC2764345.
14. Kalsotra A, Xiao X, Ward AJ, Castle JC, Johnson JM, Burge CB, et al. A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(51):20333–8. Epub 2008/12/17. doi: 10.1073/pnas.0809045105 19075228; PubMed Central PMCID: PMC2629332.
15. Karijolich J, Yu YT. Spliceosomal snRNA modifications and their function. RNA biology. 2010;7(2):192–204. Epub 2010/03/11. doi: 10.4161/rna.7.2.11207 20215871; PubMed Central PMCID: PMC4154345.
16. Bratkovic T, Rogelj B. Biology and applications of small nucleolar RNAs. Cellular and molecular life sciences: CMLS. 2011;68(23):3843–51. Epub 2011/07/13. doi: 10.1007/s00018-011-0762-y 21748470.
17. Dong Z-W, Shao P, Diao L-T, Zhou H, Yu C-H, Qu L-H. RTL-P: a sensitive approach for detecting sites of 2′-O-methylation in RNA molecules. Nucleic Acids Research. 2012;40(20):e157–e. doi: 10.1093/nar/gks698 PMC3488209. 22833606
18. snoRNABase. U94. Available from: https://www-snorna.biotoul.fr/plus.php?id=U94.
19. SnoRNABase. U6. Available from: https://www-snorna.biotoul.fr/guide.php?rna=U6.
20. Maden BE, Corbett ME, Heeney PA, Pugh K, Ajuh PM. Classical and novel approaches to the detection and localization of the numerous modified nucleotides in eukaryotic ribosomal RNA. Biochimie. 1995;77(1–2):22–9. Epub 1995/01/01. doi: 10.1016/0300-9084(96)88100-4 7599273.
21. Mann-Whitney U Calculator. Available from: https://www.socscistatistics.com/tests/mannwhitney/default3.aspx.
22. Springs UoCC. Effect-Size Calulator. Available from: https://www.uccs.edu/lbecker/.
23. Bittel DC, Butler MG, Kibiryeva N, Marshall JA, Chen J, Lofland GK, et al. Gene expression in cardiac tissues from infants with idiopathic conotruncal defects. BMC medical genomics. 2011;4:1. Epub 2011/01/07. doi: 10.1186/1755-8794-4-1 21208432; PubMed Central PMCID: PMC3023653.
24. LifeNet Health. Available from: https://www.lifenethealth.org/.
25. Matter N, König H. Targeted ‘knockdown’ of spliceosome function in mammalian cells. Nucleic Acids Research. 2005;33(4):e41–e. doi: 10.1093/nar/gni041 15731334
26. Robb GB, Brown KM, Khurana J, Rana TM. Specific and potent RNAi in the nucleus of human cells. Nature Structural &Amp; Molecular Biology. 2005;12:133. doi: 10.1038/nsmb886 15643423
Článek vyšel v časopise
PLOS One
2019 Číslo 12
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Je libo čepici místo mozkového implantátu?
- Pomůže v budoucnu s triáží na pohotovostech umělá inteligence?
- AI může chirurgům poskytnout cenná data i zpětnou vazbu v reálném čase
- Nová metoda odlišení nádorové tkáně může zpřesnit resekci glioblastomů
Nejčtenější v tomto čísle
- Methylsulfonylmethane increases osteogenesis and regulates the mineralization of the matrix by transglutaminase 2 in SHED cells
- Oregano powder reduces Streptococcus and increases SCFA concentration in a mixed bacterial culture assay
- The characteristic of patulous eustachian tube patients diagnosed by the JOS diagnostic criteria
- Parametric CAD modeling for open source scientific hardware: Comparing OpenSCAD and FreeCAD Python scripts
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy