snoRNAs are deregulated in patients with Parkinson’s Disease

Yıl 2023, Cilt 16, Sayı 1, 111 - 119, 31.01.2023

Pervin Elvan TOKGÜN Ayşe Gaye TOMATIR Fatma Gizem SARIEKİZ Sinan BİR

https://doi.org/10.31362/patd.1218005

Öz

Purpose: Small nucleolar RNAs are ranging from 65 to 300 nucleotides in length that mediate post-transcriptional
RNA modifications. They don’t have a 5′-Cap and a poly-A tail and are categorized as C/D box snoRNAs, H/
ACA box snoRNAs, and small Cajal body-specific RNAs. snoRNAs have essential roles in important biological
processes such as transcription, RNA splicing, cell cycle, and etc. In this study, we tried to reveal differential
expressions of snoRNAs in PBMCs of patients with Parkinson’s Disease by microarray analysis.
Materials and methods: Patients (n=3) who are considered to have a unilateral onset history and a good
response to dopaminergic treatment in the first years were included in the study. 10 ml peripheral blood sample
was taken for peripheral blood mononuclear cell isolation. Total RNA was extracted using GeneAll® Hybrid-R™
kit and microarray analysis was performed by using Affymetrix GeneChip Human ST 2.0 platform. Raw data
were extracted using Affymetrix Command Console Software 1.1. KEGG pathway and GO terms analyses were
performed and protein-protein interaction of host genes were determined by using STRING database.
Results: Data from patients revealed that there were 28 snoRNAs were downregulated and 3 snoRNAs were
upregulated.
Conclusion: Here in this study, we evaluated the differential expressions of snoRNAs in patients with a definitive
diagnosis of PD by microarray analysis and observed deregulated expressions of some snoRNAs. Differential
expression of snoRNA may cause changes in the transcriptional activity of host genes and thus can serve as
biomarkers for diseases.

Anahtar Kelimeler

parkinson, snoRNA, microarray

Parkinson tanısı almış hastalarda snoRNA’ların deregülasyonu

Öz

modifikasyonlarına aracılık ederler. 5'-uçları ve poli-A kuyrukları yoktur. C/D box snoRNA'lar, H/ACA box
snoRNA'lar ve küçük kajal gövdesine özgü RNA'lar olarak sınıflandırılırlar. snoRNA'lar, transkripsiyon, RNA
eklenmesi, hücre döngüsü vb. gibi önemli biyolojik süreçlerde önemli rollere sahiptir. Bu çalışmada, Parkinson
tanısı alan hastaların PBMC'lerinde snoRNA'ların ifade değişimlerini mikroarray analizi ile ortaya koymaya
çalıştık.
Gereç ve yöntem: Unilateral başlangıç öyküsü olan ve ilk yıllarda dopaminerjik tedaviye iyi yanıt verdiği
düşünülen hastalar (n=3) çalışmaya alındı. Periferik kan mononükleer hücre izolasyonu için 10 ml periferik kan
örneği alındı. Total RNA, GeneAll® Hybrid-R™ kiti kullanılarak izole edildi ve Affymetrix GeneChip Human ST
2.0 platformu kullanılarak mikrodizin analizi yapıldı. Ham datalar, Affymetrix Command Console Software 1.1
kullanılarak çıkarıldı. KEGG yolak ve Gen ontoloji analizleri yapıldı ve lokus genlerin protein-protein değişimi
STRING veri tabanı kullanılarak gerçekleştirildi.
Bulgular: Elde edilen veriler, 28 snoRNA'nın upregüle olduğunu ve 3 snoRNA'nın downregüle olduğunu ortaya
çıkardı
Sonuç: Bu çalışmada, mikrodizin analizi ile kesin Parkinson tanısı alan hastalarda snoRNA'ların ifade
değişimlerini değerlendirdik ve bazı snoRNA'ların deregüle ekspresyonlarını gözlemledik. snoRNA'lardaki ifade
değişimi, lokus genlerin transkripsiyonel aktivitesinde değişikliklere neden olabilir ve bu nedenle hastalıklar için
biyobelirteçler olarak değerlendirilebilirler.

Anahtar Kelimeler

parkinson, snoRNA, mikrodizin

Kaynakça

• 1. Kiss T. Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs. EMBO J 2001;20:3617-3622. https://doi.org/10.1093/emboj/20.14.3617
• 2. Dieci G, Preti M, Montanini B. Eukaryotic snoRNAs: a paradigm for gene expression flexibility. Genomics 2009;94:83-88. https://doi.org/10.1016/j.ygeno.2009.05.002
• 3. Brown JW, Marshall DF, Echeverria M. Intronic noncoding RNAs and splicing. Trends Plant Sci 2008;13:335-342. https://doi.org/10.1016/j.tplants.2008.04.010
• 4. Liang J, Wen J, Huang Z, et al. Small nucleolar RNAs: ınsight ınto their function in cancer. Front Oncol 2019;9:587. https://doi.org/10.3389/fonc.2019.00587
• 5. Hüttenhofer A, Brosius J, Bachellerie JP. RNomics: identification and function of small, non-messenger RNAs. Curr Opin Chem Biol 2002;6:835-843. https://doi.org/10.1016/s1367-5931(02)00397-6
• 6. Wajahat M, Bracken CP, Orang A. Emerging functions for snoRNAs and snoRNA-derived fragments. Int J Mol Sci 2021;22:10193. https://doi.org/10.3390/ijms221910193
• 7. Wei JW, Huang K, Yang C, et al. Non-coding RNAs as regulators in epigenetics (Review). Oncol Rep 2017;37:3-9. https://doi.org/10.3892/or.2016.5236
• 8. Ender C, Krek A, Friedländer MR, et al. A human snoRNA with microRNA-like functions. Mol Cell 2008;32:519-528. https://doi.org/10.1016/j.molcel.2008.10.017
• 9. Erro R, Stamelou M. The motor syndrome of parkinson’s disease. Int Rev Neurobiol 2017;132:25-32. https://doi.org/10.1016/bs.irn.2017.01.004
• 10. Greenland JC, Williams Gray CH, Barker RA. The clinical heterogeneity of Parkinson's disease and its therapeutic implications. Eur J Neurosci 2019;49:328-338. https://doi.org/10.1111/ejn.14094
• 11. Kang H, Shin JH. Repression of rRNA transcription by PARIS contributes to Parkinson's disease. Neurobiol Dis 2015;73:220-228. https://doi.org/10.1016/j.nbd.2014.10.003
• 12. Dsouza VL, Adiga D, Sriharikrishnaa S, et al. Small nucleolar RNA and its potential role in breast cancer - A comprehensive review. Biochim Biophys Acta Rev Cancer 2021;1875:188501. https://doi.org/10.1016/j.bbcan.2020.188501
• 13. Gstir R, Schafferer S, Scheideler M, et al. Generation of a neuro-specific microarray reveals novel differentially expressed noncoding RNAs in mouse models for neurodegenerative diseases. RNA 2014;20:1929-1943. https://doi.org/10.1261/rna.047225.114
• 14. Jiao FJ, Wang QZ, Zhang P, et al. CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson's disease model. Sci Rep 2017;7:5622. https://doi.org/10.1038/s41598-017-06012-6
• 15. Cavaillé J, Buiting K, Kiefmann M, et al. Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc Natl Acad Sci U S A 2000;97:14311-14316. https://doi.org/10.1073/pnas.250426397
• 16. Bluth M, Lin YY, Zhang H, Viterbo D, Zenilman M. Use of gene expression profiles in cells of peripheral blood to identify new molecular markers of acute pancreatitis. Arch Surg 2008;143:227-233;discussion 233-234. https://doi.org/10.1001/archsurg.2007.73
• 17. Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther 2008;10:101. https://doi.org/10.1186/ar2493
• 18. Baine MJ, Chakraborty S, Smith LM, et al. Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility. PLoS One 2011;6:17014. https://doi.org/10.1371/journal.pone.0017014