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Review
. 2017 Jun 3;14(6):693-700.
doi: 10.1080/15476286.2016.1249091. Epub 2016 Oct 24.

RNA modification in Cajal bodies

U Thomas Meier  1
Affiliations
Review

RNA modification in Cajal bodies

U Thomas Meier. RNA Biol. .

Abstract

Aside from nucleoli, Cajal bodies (CBs) are the best-characterized organelles of mammalian cell nuclei. Like nucleoli, CBs concentrate ribonucleoproteins (RNPs), in particular, spliceosomal small nuclear RNPs (snRNPs) and small nucleolar RNPs (snoRNPs). In one of the best-defined functions of CBs, most of the snoRNPs are involved in site-specific modification of snRNAs. The two major modifications are pseudouridylation and 2'-O-methylation that are guided by the box H/ACA and C/D snoRNPs, respectively. This review details the modifications, their function, the mechanism of modification, and the machineries involved. We dissect the different classes of noncoding RNAs that meet in CBs, guides and substrates. Open questions and conundrums, often raised and appearing due to experimental limitations, are pointed out and discussed. The emphasis of the review is on mammalian CBs and their function in modification of noncoding RNAs.

Keywords: 2′-O-methyl; C/D RNA; Cajal body; H/ACA RNA; pseudouridine; scaRNA; snRNA; snoRNA; spliceosomal; telomerase.

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Figures

Figure 1.
Figure 1.
SnoRNAs and life cycle. (A) List of small nucleolar RNAs (snoRNAs) and ribonucleoprotein (RNP) core proteins. Abbreviations: small Cajal body (CB)-specific (sca) and human telomerase RNA (hTR). (B) Schematic of snoRNA mode of expression, trafficking, and sites of action and that of its main target in CBs, spliceosomal small nuclear RNAs (snRNAs). See text for full explanation. Pseudouridylation and 2′-O-methylation modifications are indicated (asterisks). Note proteins were left off for simplicity and clarity.
Figure 2.
Figure 2.
Modifications and scaRNAs. (A) Schematic of pseudouridylation (red) and 2′-O-methylation (green). Note although indicated on the same nucleoside, these are independent modification reactions. (B) H/ACA scaRNA with CB localizing elements (CAB) and a substrate RNA in one of the 2 pseudouridylation pockets. Note CAB boxes and guide elements can reside in one or the other hairpin or both. (C) C/D scaRNA with a CB localizing G•U/U•G wobble stem (G•U) and 2 substrate RNAs. Note the fifth nucleotide of the substrate from boxes D and/or D′ is targeted for 2′-O-methylation (CH3).
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