2'-O-Methylation
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2'-O-methylation is a common nucleoside modification of RNA, where a methyl group is added to the 2' hydroxyl group of the ribose moiety of a nucleoside. 2'-O-methylated nucleosides are mostly found in ribosomal RNA and small nuclear RNA and occur in the functionally essential regions of the ribosome and splicesome.[1] Also, 2'-O-methylation of adenosine in an RNA prevents adenosine deaminase from editing it to an inosine.[2]
Recently a novel method to map 2'-O ribose methylations by high throughput sequencing has been published. [3] The method is quantitative and maps all modifications in a single experiment.
Functions edit
In general, 2'-O-methylation is a common post-transcriptional modification of naturally occurring stable RNAs.
tRNAs edit
2'-O-methylation only occurs at certain positions (e.g. on first nucleotide of tRNA1-Ser's anticodon) to stabilize the codon-anticodon duplex, and in vitro experiments indicate that at other locations (e.g. on second or third nucleotide of tRNA1-Ser's anticodon) 2'-O-methylation disrupts codon-reading activity[4]. Anticodon of eucaryotic tRNA-Phe has 2'-O-methylated cytidine and guanosine at positions 32 and 34, which are involved in frameshift maintenance[5]. A recent study also links defective 2'-O-methylation at these two locations to loss-of-function of FTSJ1 gene, which causes nonsyndromic X-linked intellectual disability[6].
mRNAs edit
Many eukaryotes have their mRNAs 2'-O-methylated at 5' cap, but their function remains largely unknown. Certain viruses that operate in eukaryotes have also evolved with 2'-O-methylation at 5' cap which allows them to evade innate host immune responses. Usually detectors in cytosol, such as Mda5, initiate the signaling cascades if viral RNA is present, and interferons, a group of signaling proteins, notify neighbouring cells. Viruses with 2'-O-methylation at 5' cap, such as West Nile viruses, have a much smaller chance of inducing high interferon expression, which suggests 2'-O-methylation is a mechanism involved in distinguishing between self and non-self (e.g. viral) mRNAs[7].
rRNAs edit
2'-O-methylation is an indispensable step in ribosome biogenesis. With the help of snoRNAs, whose roles are guides for the 2'-O-methylation of rRNAs, rRNA precursor can be cleaved to become subunits, and to be exported from nucleus to cytoplasm for ribosome assembly[8].
miRNAs edit
A miRNA is a small non-coding RNA molecule that acts as RNA silencer. Plant miRNAs undergo 3'-end 2'-O-methylation, which is essential for their maturation and stability[9]. In Drosophila, a genus of flies, positive correlation between age and 2'-O-methylation has been found[10].
piRNAs edit
In animals, piRNAs, small non-coding RNA molecules slightly larger than miRNAs, are 2'-O-methylated at 3' end as a tag to stop further nucleotide addition and to stabilize themselves[11].
References edit
- ^ Kiss T (2001). "Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs". EMBO J. 20 (14): 3617–3622. doi:10.1093/emboj/20.14.3617. PMC 125535. PMID 11447102.
- ^ Beal PA, Maydanovych O, Pokharel S (2007). "The chemistry and biology of RNA editing by adenosine deaminases". Nucleic Acids Symposium Series. 51 (1): 83–84. doi:10.1093/nass/nrm042. PMID 18029597.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Birkedal U; et al. (2015). "Profiling of Ribose Methylations in RNA by High-Throughput Sequencing". Angew. Chem. Int. Ed. 54 (2): 451–455. doi:10.1002/anie.201408362. PMID 25417815.
{{cite journal}}: Explicit use of et al. in:|author=(help) - ^ Satoh, A; Takai, K; Ouchi, R; Yokoyama, S; Takaku, H (May 2000). "Effects of anticodon 2'-O-methylations on tRNA codon recognition in an Escherichia coli cell-free translation". RNA (New York, N.Y.). 6 (5): 680–686. PMID 10836789.
- ^ Agris, P. F. (2 January 2004). "Decoding the genome: a modified view". Nucleic Acids Research. 32 (1): 223–238. doi:10.1093/nar/gkh185.
- ^ Guy, MP; Shaw, M; Weiner, CL; Hobson, L; Stark, Z; Rose, K; Kalscheuer, VM; Gecz, J; Phizicky, EM (27 August 2015). "Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicated in Nonsyndromic X-Linked Intellectual Disability due to Mutations in FTSJ1". Human mutation. PMID 26310293.
- ^ Li, J; Zhang, Y. "10". In Dricu, A (ed.). Methylation - From DNA, RNA and Histones to Diseases and Treatment. InTech. pp. 257–258. ISBN 978-953-51-0881-8.
- ^ Kressler, Dieter; Hurt, Ed; Babler, Jochen (2009). "Driving ribosome assembly". Biochima et Biophysica Acta. 1803: 673–683. doi:10.1016/j.bbamcr.2009.10.009. Retrieved 20 November 2014.
- ^ Ji, L; Chen, X (April 2012). "Regulation of small RNA stability: methylation and beyond". Cell research. 22 (4): 624–36. PMID 22410795.
- ^ Abe, M; Naqvi, A; Hendriks, GJ; Feltzin, V; Zhu, Y; Grigoriev, A; Bonini, NM (1 January 2014). "Impact of age-associated increase in 2'-O-methylation of miRNAs on aging and neurodegeneration in Drosophila". Genes & development. 28 (1): 44–57. PMID 24395246.
- ^ Suzuki, T; Miyauchi, K; Sakaguchi, Y; Suzuki, T (2014). "Biochemical and mass spectrometric analysis of 3'-end methylation of piRNAs". Methods in molecular biology (Clifton, N.J.). 1093: 59–72. PMID 24178557.