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snoRNA Research

What Are snoRNAs and Why Study Them?

 

Small nucleolar RNAs (snoRNAs) are intermediate-length small noncoding RNAs (sncRNAs), ranging from 60 to 300 nt. They are a vital component of small nucleolar ribonucleoprotein (snoRNPs) [1]. In vertebrates, the snoRNA genes are frequently embedded within the introns of protein coding genes and post-transcriptionally processed [2]. snoRNAs are involved in rRNA processing and regulation of splicing, translation, and oxidative stress [3]. Within snoRNPs, snoRNAs complement with rRNA sequences and guide the modification of 2’ O-methylation or pseudouridylation. RNPs that catalyze 2’ O-methylation are called C/D box RNPs, while those that catalyze pseudouridylation are termed H/ACA box RNPs [1]. Besides these snoRNAs, small Cajal body-specific RNAs (scaRNA) in the primary structures of small Cajal body in the nucleus frequently contain similar box C/D and box H/ACA domains. They are structurally indistinguishable from canonical snoRNAs [4]. Also, some snoRNAs can be processed by Dicer and give rise to miRNA-like RNAs, capable of binding to AGO and complementing with mRNA and thus regulating the translation [5]. 

Dysregulated expression of snoRNAs in cancer and their roles in metastasis are well documented. SnoRNAs can act either as tumor promoters or suppressors [6-7]. For example, SNORD50A/B act as tumor suppressors which directly bind and inhibit K-Ras and are recurrently deleted in human cancer [8]; SNORD44 (RNU44) and SNORD43 (RNU43) are associated with poor prognosis of breast cancer [9]; and SNORA80E (SNORA42) can act as oncogene in lung cancer and its siRNA knock down has shown anti-cancer effects [10]. Interestingly, C/D box snoRNAs are globally increased in cancer [11]. snoRNA expression is also dysregulated in neurodegenerative disorders. snoRNAs are relatively stable and have been detected in blood plasma, sputum, and urine samples, presenting a promising biomarkers for diagnostics and targets for treatment. Studying snoRNAs has become a vibrant field of research.


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References
1. Esteller M. (2011) "Non-coding RNAs in human disease." Nat. Rev. Genet. 12(12):861-74 [PMID: 22094949]2. Richard P. and T. Kiss (2006) "Integrating snoRNP assembly with mRNA biogenesis." EMBO Rep. 7(6):590-2 [PMID: 16741502]
3. Williams G.T. and F. Farzaneh (2012) "Are snoRNAs and snoRNA host genes new players in cancer?" Nat. Rev. Cancer 12(2):84-8 [PMID: 22257949]
4. Darzacq X. et al. (2002) "Cajal body-specific small nuclear RNAs: a novel class of 2'-O-methylation and pseudouridylation guide RNAs." EMBO J. 21(11):2746-56 [PMID: 12032087]
5. Ender C. et al. (2008) "A human snoRNA with microRNA-like functions." Mol. Cell 32(4):519-28 [PMID: 19026782]
6. Nallar S.C. and D.V. Kalvakolanu (2013) "Regulation of snoRNAs in cancer: close encounters with inter*****." J. Inter***** Cytokine Res. 33(4):189-98 [PMID: 23570385]
7. Mannoor K. et al. (2012) "Small nucleolar RNAs in cancer." Biochim. Biophys. Acta 1826(1):121-8 [PMID: 22498252]
8. Siprashvili Z. et al. (2016) "The noncoding RNAs SNORD50A and SNORD50B bind K-Ras and are recurrently deleted in human cancer." Nat. Genet. 48(1):53-8 [PMID: 26595770]
9. Gee H.E. et al. (2011) "The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis." Br. J. Cancer 104(7):1168-77 [PMID: 21407217]
10. Mei Y.P. et al. (2012) "Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis." Oncogene 31(22):2794-804 [PMID: 21986946]
11. Su H. et al. (2014) "Elevated snoRNA biogenesis is essential in breast cancer." Oncogene 33(11):1348-58 [PMID: 23542174]

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